PI3K/Akt/mTOR

CCL17 exerts neuroprotection through activation of CCR4/mTORC2 axis in microglia after subarachnoid haemorrhage in rats

25 | Jan 26 2024

This study elucidates that CCL17 activates the CCR4/mTORC2 axis in microglia, promoting M2-like polarization and significantly ameliorating neurological deficits after subarachnoid hemorrhage. [Read the Full Post]

Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201

63 | Jan 22 2024

Targeting the SUV39H1-H3K9me3 pathway in DIPG cells with chaetocin, and combining it with a DRD2 antagonist like ONC201, presents a promising strategy for effective treatment by exploiting vulnerabilities and overcoming resistance mechanisms. [Read the Full Post]

Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study

46 | Jan 21 2024

The study utilizing Mendelian randomization suggests a causal link between longer leukocyte telomere length and a reduced risk of systemic sclerosis, implicating the influence of specific genetic variants in TERC and TERT genes. [Read the Full Post]

Drug Repositioning Identifies Six Drug Candidates for Systemic Autoimmune Diseases by Integrative Analyses of Transcriptomes from Scleroderma, Systemic Lupus Erythematosus, and Sjogren's Syndrome

0 | Jan 18 2024

This study utilizing transcriptome data and bioinformatic analysis identified common gene signatures across systemic autoimmune diseases, leading to the discovery of six potential small molecule drug candidates through drug repositioning, shedding light on novel therapeutic avenues for these conditions. [Read the Full Post]

AT7867 promotes pancreatic progenitor differentiation of human iPSCs

44 | Jan 18 2024

AT7867 treatment significantly enhances the differentiation of pancreatic progenitor cells, resulting in increased expression of key markers and accelerated diabetes reversal upon transplantation into diabetic mice. [Read the Full Post]

Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer's Disease

12 | Jan 15 2024

Your study on repurposed drugs for Alzheimer's disease highlights promising candidates like clomiphene citrate and Pik-90, signaling a step forward in bridging computational predictions with experimental validation. [Read the Full Post]

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

33 | Jan 14 2024

PP121, a dual tyrosine and phosphoinositide kinase inhibitor, demonstrates promising anti-contractile and anti-inflammatory effects in asthma treatment, suggesting its potential as a novel therapeutic compound for managing the condition. [Read the Full Post]

MTX-211 Inhibits GSH Synthesis through Keap1/NRF2/GCLM Axis and Exerts Antitumor Effects in Bladder Cancer

44 | Jan 10 2024

MTX-211 demonstrates promising potential as a therapeutic agent for bladder cancer by inhibiting cell proliferation through the Keap1/NRF2/GCLM signaling pathway and depleting intracellular GSH levels. [Read the Full Post]

The mitochondrial NADH shuttle system is a targetable vulnerability for Group 3 medulloblastoma in a hypoxic microenvironment

25 | Jan 08 2024

Research examining metabolic pathways in Group 3 medulloblastoma cells has unveiled promising therapeutic strategies, showcasing inhibitors that target NADH shuttles and mitochondrial function, offering hope for more effective treatments in this aggressive tumor subtype. [Read the Full Post]

Percutaneous coronary intervention with ridaforolimus-eluting stents in long lesions: the BIONICS 38 mm prospective trial

49 | Jan 08 2024

The study evaluating the 38 mm ridaforolimus-eluting stent in percutaneous coronary intervention for long lesions demonstrated high efficacy, low rates of major adverse cardiovascular events, and successful treatment outcomes, supporting its safety and effectiveness in this patient group. [Read the Full Post]

Sertad1 Induces Neurological Injury after Ischemic Stroke via the CDK4/p-Rb Pathway

96 | Jan 06 2024

Sertad1, upregulated in ischemic conditions, exacerbates neurological injury by activating the CDK4/p-Rb pathway, promoting cell cycle dysregulation and apoptotic cell death. [Read the Full Post]

Quantitative Proteomics Characterization of the Effect and Mechanism of Trichostatin A on the Hippocampus of Type II Diabetic Mice

36 | Jan 03 2024

The study demonstrates Trichostatin A's potential in improving cognitive function in diabetic encephalopathy by modulating key proteins and pathways, highlighting its promise as a therapeutic intervention and suggesting potential similar and ancillary drugs for treatment. [Read the Full Post]

Comprehensive analysis of angiogenesis pattern and related immune landscape for individual treatment in osteosarcoma

31 | Jan 01 2024

The ANGscore, a novel prognostic model based on angiogenesis patterns in osteosarcoma, not only accurately predicts patient outcomes and immune characteristics but also holds promise in guiding personalized treatment strategies and immunotherapy responses for better clinical management. [Read the Full Post]

Translating in vitro CFTR rescue into small molecule correctors for cystic fibrosis using the Library of Integrated Network-based Cellular Signatures drug discovery platform

38 | Dec 29 2023

Research employing transcriptomic signatures from CF expression data and LINCS in silico screening identified XL147, among other compounds, as a promising candidate for partially restoring ΔF508-CFTR function, showing efficacy in primary CF airway epithelia and demonstrating potential for improved CF corrector therapies. [Read the Full Post]

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats

51 | Dec 29 2023

Exposure to ethanol, THC, or their combination during adolescence in rats resulted in reduced body weight gain, altered substance intake, and disrupted long-term depression in the medial prefrontal cortex, potentially implicating lasting changes in GABA and GSK3β signaling pathways. [Read the Full Post]

LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression

15 | Dec 28 2023

The HOTAIR/miR-145-5p/NUAK1 axis, identified through its intricate epigenetic regulation and influence on the EMT process in liver cancer cells, holds promise as both a prognostic biomarker and a potential therapeutic target. [Read the Full Post]

Dysregulation of the Progranulin-driven Autophagy-lysosomal Pathway Mediates Secretion of the Nuclear Protein TDP-43

40 | Dec 27 2023

Dysregulation of the progranulin-driven autophagy-lysosomal pathway promotes the secretion of TDP-43, potentially fueling its cell-to-cell spread in neurodegenerative diseases like amyotrophic lateral sclerosis and frontotemporal lobar degeneration. [Read the Full Post]

PM2.5 induces cardiac malformations via PI3K/akt2/mTORC1 signaling pathway in zebrafish larvae

82 | Dec 27 2023

Exposure to PM2.5 triggers a complex cascade involving PI3K/akt2/mTORC1 signaling through AHR/ROS-induced PTEN suppression, leading to mitochondrial-mediated intrinsic apoptosis, Wnt signaling suppression, and ultimately contributing to cardiac defects in zebrafish larvae. [Read the Full Post]

Nanoparticles overcome adaptive immune resistance and enhance immunotherapy via targeting tumor microenvironment in lung cancer

27 | Dec 25 2023

"Through nanoparticle-based modulation of the tumor microenvironment, this review underscores a promising avenue to overcome immune resistance to PD-1/PD-L1 blockade in lung cancer, potentially revolutionizing the landscape of immunotherapy for these patients." [Read the Full Post]

AZ32 Reverses ABCG2-Mediated Multidrug Resistance in Colorectal Cancer

40 | Dec 22 2023

The study established that the ATM kinase inhibitor AZ32 effectively sensitizes ABCG2-overexpressing colorectal cancer cells to chemotherapeutic drugs, such as mitoxantrone and doxorubicin, by retaining them inside cells, thus demonstrating its potential to reverse ABCG2-mediated multidrug resistance. [Read the Full Post]

Open-Label, Multicenter, Randomized, Biomarker-Integrated Umbrella Trial for Second-Line Treatment of Advanced Gastric Cancer: K-Umbrella Gastric Cancer Study

21 | Dec 15 2023

This controlled umbrella trial demonstrated the feasibility of IHC-based screening for druggable targets in HER2-negative advanced gastric cancer, with targeted agents in the biomarker group showing mixed efficacy, indicating the potential for early screening of novel therapies in specific subgroups. [Read the Full Post]

Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma

67 | Dec 13 2023

In summary, the study reveals that inhibiting phosphorylated S6 ribosomal protein, a marker of mTORC1 activity, suppresses glucose metabolism pathways and reduces cell proliferation, suggesting mTORC1 as a potential therapeutic target in distal cholangiocarcinoma. [Read the Full Post]

Pharmacological effects of mTORC1/C2 inhibitor in a preclinical model of NASH progression

21 | Dec 13 2023

The study demonstrates that the mTORC1/C2 inhibitor Ku-0063794 (KU) effectively alleviates NASH-related hepatotoxicity, reduces oxidative stress, modulates gene expression, and decreases inflammation in a mouse model, highlighting its potential as a therapeutic candidate for non-alcoholic steatohepatitis. [Read the Full Post]

MLN4924 inhibits hedgehog signaling pathway and activates autophagy to alleviate mouse laser-induced choroidal neovascularization lesion

0 | Dec 11 2023

MLN4924, a selective inhibitor of NEDD8-activating enzyme, mitigates neovascular age-related macular degeneration by inhibiting choroidal neovascularization through the upregulation of hedgehog pathway-regulated autophagy in choroidal endothelial cells under hypoxia conditions. [Read the Full Post]

Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition

32 | Dec 09 2023

**LPS-induced inhibition of autophagy leads to trigeminal ganglion neurite loss, highlighting a potential therapeutic target for corneal nerve damage.** [Read the Full Post]

Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models

60 | Dec 07 2023

The study demonstrates that ABTL0812, an oral anticancer compound, inhibits GBM cell proliferation, reverses proneural to mesenchymal transition, induces cell differentiation, and promotes autophagy-mediated cell death, providing compelling evidence for its potential as a novel therapy, either alone or in combination with standard treatments, for glioblastoma multiforme. [Read the Full Post]

Cantharidin induces senescence via inhibition of AMP-activated protein kinase and activation of NLRP3 inflammasome in H9c2 cardiomyocytes

12 | Dec 07 2023

Cantharidin induces cardiomyocyte senescence and senescence-associated secretory phenotype (SASP) through activation of the NLRP3 inflammasome and inhibition of AMPK phosphorylation, providing novel insights into its cardiotoxic effects. [Read the Full Post]

Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in KRAS-Mutant Pancreatic and Colorectal Cancer

22 | Dec 01 2023

The discovery of borussertib, a covalent-allosteric AKT inhibitor, and its demonstrated efficacy in combination with the MEK inhibitor trametinib in patient-derived xenograft models represent a promising advancement in targeted cancer therapy for individuals with specific genetic alterations in the PTEN, PI3K, and RAS signaling pathways. [Read the Full Post]

Indication for a Pneumocystis Prophylaxis Therapy in Patients with Vascular Anomalies Treated with PIK3/AKT/mTOR Pathway Inhibitors: Experts' Opinion and Systematic Review from the Literature

21 | Nov 27 2023

The study underscores the rare but existing risk of Pneumocystis jirovecii pneumonia in patients with vascular anomalies treated with mTOR inhibitors, indicating the potential benefit of prophylaxis, particularly with trimethoprim-sulfamethoxazole, for specific high-risk patient groups. [Read the Full Post]

Pharmacological Inhibition of PTEN Rescues Dopaminergic Neurons by Attenuating Apoptotic and Neuroinflammatory Signaling Events

18 | Nov 24 2023

The discovery that PTEN serves as a critical early stress sensor, modulating Fyn kinase activation, mitochondrial dysfunction, and neuroinflammation, establishes it as a promising pharmacological target for the development of novel therapeutic strategies in Parkinson's disease. [Read the Full Post]

Oridonin Synergistically Enhances the Pro-Apoptotic Effect of Venetoclax on Acute Myeloid Leukemia Cells by Inhibiting AKT Signaling

27 | Nov 23 2023

**Synergistic inhibition of AKT signaling by oridonin enhances the apoptotic effects of venetoclax, offering a promising combination therapy to overcome resistance and improve outcomes in acute myeloid leukemia.** [Read the Full Post]

Reconstructing the immunosenescence core pathway reveals global characteristics in pan-cancer

25 | Nov 20 2023

Your study systematically analyzed multi-omics data from 12,836 tumor samples, revealing disordered immunosenescence pathways across cancer types, emphasizing the pan-cancer activation of immunosenescence pathways, and identifying the MTOR gene as a potential sex-specific immunosenescence biomarker in head and neck squamous carcinoma, suggesting OSI-027 as a promising sex-specific drug. [Read the Full Post]

Inhibition of growth and contraction in human prostate stromal cells by silencing of NUAK1 and -2, and by the presumed NUAK inhibitors HTH01-015 and WZ4003

17 | Nov 14 2023

NUAK1 and NUAK2 promote cell survival and proliferation in prostate stromal cells, potentially contributing to stromal hyperplasia in benign prostatic hyperplasia (BPH), and their effects can be mimicked by inhibitors HTH01-015 and WZ4003, suggesting therapeutic relevance in BPH management. [Read the Full Post]

Inaugural Results of the Individualized Screening Trial of Innovative Glioblastoma Therapy: A Phase II Platform Trial for Newly Diagnosed Glioblastoma Using Bayesian Adaptive Randomization

39 | Nov 13 2023

The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) is a phase II platform trial that employs genomic profiling and adaptive randomization to evaluate novel therapies for glioblastoma, with abemaciclib and neratinib showing improved progression-free survival compared to the control arm, although none of the experimental therapies demonstrated a significant overall survival benefit. [Read the Full Post]

Scutellarin suppresses the metastasis of triple-negative breast cancer via targeting TNFα/TNFR2-RUNX1-triggered G-CSF expression in endothelial cells

135 | Nov 13 2023

Scutellarin (SC) inhibits metastasis in triple-negative breast cancer (TNBC) by disrupting the TNFα/TNFR2-initiated RUNX1 activation and subsequent G-CSF production in TNBC-associated endothelial cells (ECs). [Read the Full Post]

Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study

34 | Nov 11 2023

The combination of tenalisib and romidepsin showed promising efficacy with a 63.0% overall objective response rate in patients with relapsed/refractory T-cell lymphoma, along with a manageable safety profile, supporting its further development as a potential treatment option. [Read the Full Post]

VPS34-IN1 induces apoptosis of ER+ breast cancer cells via activating PERK/ATF4/CHOP pathway

0 | Nov 06 2023

VPS34-IN1, a selective inhibitor of Class III Phosphatidylinositol 3-kinase (PI3K), exhibits an antitumor effect in estrogen receptor positive (ER+) breast cancer by activating the PERK/ATF4/CHOP pathway of endoplasmic reticulum (ER) stress, leading to apoptosis of breast cancer cells. [Read the Full Post]

Silencing of RhoC induces macrophage M1 polarization to inhibit migration and invasion in colon cancer via regulating the PTEN/FOXO1 pathway

25 | Nov 04 2023

This study shows that silencing RhoC in colon cancer cells reduces invasion, migration, and tumor growth by suppressing M2 macrophage polarization and modulating the PTEN/FOXO1 pathway. [Read the Full Post]

Production of highly pure R,R-2,3-butanediol for biological plant growth promoting agent using carbon feeding control of Paenibacillus polymyxa MDBDO

65 | Nov 03 2023

The study demonstrates the potential of Paenibacillus polymyxa MDBDO as a biological plant growth promoting agent and outlines a fermentation strategy for the production of highly pure R,R-2,3-butanediol (R,R-2,3-BDO) at high concentrations, which significantly stimulates the growth of soybean and strawberry seedlings. [Read the Full Post]

[6]-Gingerol induces Caspase-Dependent Apoptosis in Bladder Cancer cells via MAPK and ROS Signaling

15 | Oct 30 2023

[6]-Gingerol ([6]-GIN) induces apoptosis in bladder cancer cells, inhibiting cell proliferation, disrupting mitochondrial function, regulating key proteins and enzymes involved in cell survival and death, activating MAPKs, and increasing reactive oxygen species, suggesting its potential as a promising candidate for the development of bladder cancer treatment. [Read the Full Post]

Lactobacillus rhamnosus HN001 Ameliorates BEZ235-Induced Intestinal Dysbiosis and Prolongs Cardiac Transplant Survival

17 | Oct 30 2023

The combination of the dual inhibitor BEZ235 and Lactobacillus rhamnosus HN001, along with its metabolic product propionic acid (PA), demonstrates a novel and efficient therapeutic strategy for prolonging cardiac transplant survival by suppressing the PI3K/AKT/mTOR pathway, rescuing intestinal microbiota imbalance, and enriching regulatory T cells. [Read the Full Post]

Tumor lysates-constructed hydrogel to potentiate tumor immunotherapy

35 | Oct 29 2023

An injectable tumor lysates-constructed hydrogel has been developed to address the challenges of T cell-based immunotherapy, providing a robust antigen reservoir, preventing T cell exhaustion, and suppressing immune evasion, thereby enhancing the effectiveness of tumor treatment. [Read the Full Post]

Identification of Tau-Tubulin Kinase 1 Inhibitors by Microfluidics-based Mobility Shift Assay from a Kinase Inhibitor Library

71 | Oct 29 2023

This study identified a peptide substrate for human TTBK1 and developed a microfluidics-based assay, enabling the screening of kinase inhibitors and the potential development of novel hTTBK1 inhibitors for Alzheimer's disease prevention. [Read the Full Post]

[ANMCO Expert opinion: Bempedoic acid place in therapy for hypercholesterolemia management]

39 | Oct 24 2023

Bempedoic acid, a newly approved therapeutic option for hypercholesterolemia, offers a hepatic selective action that reduces the risk of muscle adverse effects, making it particularly useful in certain clinical settings according to an ANMCO document. [Read the Full Post]

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B cell lymphoma

31 | Oct 24 2023

The study identifies EGR1-mediated metabolic reprogramming to oxidative phosphorylation as a key mechanism driving ibrutinib resistance in B cell malignancies, suggesting that targeting this pathway with agents like metformin or IM156 could provide a potential therapeutic strategy to overcome acquired drug resistance in relapsed/refractory DLBCL or MCL. [Read the Full Post]

Taselisib moderates neuropathic pain through PI3K/AKT signaling pathway in a rat model of chronic constriction injury

61 | Oct 19 2023

Taselisib treatment alleviated neuropathic pain in rats by suppressing the pro-inflammatory response and modulating the PI3K/AKT signaling pathway. [Read the Full Post]

Synthesis, Anticancer, Antimicrobial and Antioxidant Potential of Novel 4-(Substituted phenyl-1,3,4-oxadiazol/thiadiazol-2-yl)-4-(4-substituted phenyl) Azetidin-2-One Derivatives

22 | Oct 16 2023

The synthesized 4-substitutedphenyl-1,3,4-oxadiazol/Thiadiazol-2-yl)-4-(4-substitutedphenyl) azetidin-2-one derivatives demonstrated high efficacy against MCF-7 cancer cell lines, significant antimicrobial potential, and potent antioxidant activity, suggesting their potential for further research and development as therapeutic agents. [Read the Full Post]

Inhibition of PIKFYVE kinase interferes ESCRT pathway to suppress RNA virus replication

25 | Oct 13 2023

The inhibition of PIKFYVE kinase by YM201636 disrupts the ESCRT pathway and endosomal transport, leading to the repression of replication for various RNA viruses, offering potential antiviral therapy against RNA virus infections. [Read the Full Post]

ABCB1 and ABCG2 Overexpression Mediates Resistance to the Phosphatidylinositol 3-Kinase Inhibitor HS-173 in Cancer Cell Lines

51 | Oct 13 2023

The study demonstrated that HS-173, a potent PI3K inhibitor, is susceptible to efflux mediated by ABCB1 and ABCG2 transporters, leading to decreased intracellular drug concentration and suggesting potential implications for its clinical use in multidrug-resistant cancers. [Read the Full Post]

Anti-hepatocellular carcinoma activity of the cyclin-dependent kinase inhibitor AT7519

76 | Oct 07 2023

The research findings suggest that AT7519, a CDK inhibitor, shows potential as a monotherapy or in combination with drugs like gefitinib or cabozantinib, to improve the effectiveness of treatments for hepatocellular carcinoma. [Read the Full Post]

Translation-dependent skin hyperplasia is promoted by type 1/17 inflammation in psoriasis

60 | Oct 05 2023

This study reveals that the molecule eukaryotic initiation factor 4E (eIF4E) plays a crucial role in the abnormal differentiation of keratinocytes driven by type 1/17 inflammation in psoriasis, suggesting its potential as a therapeutic target. [Read the Full Post]

Up-regulation of MELK by E2F1 promotes the proliferation in cervical cancer cells

30 | Oct 03 2023

The study demonstrated that MELK plays a vital role in cervical cancer cell proliferation, and targeting MELK could be a potential therapeutic approach for the treatment of cervical cancer. [Read the Full Post]

A new CCCH-type zinc finger-related lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients

14 | Sep 30 2023

The study constructed a prognostic signature based on eight CCCH-type zinc finger-associated lncRNAs (CTZFLs) that independently predicted patient prognosis and showed potential for aiding in medication selection for clear cell renal cell carcinoma (ccRCC). [Read the Full Post]

The potent AMPK inhibitor BAY-3827 shows strong efficacy in androgen-dependent prostate cancer models

52 | Sep 24 2023

The novel and potent AMPK inhibitor BAY-3827 demonstrates strong anti-proliferative effects in androgen-dependent prostate cancer cell lines, upregulates genes involved in lipid metabolism, and inhibits key components of the lipid flux pathway, providing valuable insights into the role of AMPK signaling in cancer, especially in prostate cancer. [Read the Full Post]

Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): Clinical candidate for cancer therapy

99 | Sep 17 2023

VX-970 (berzosertib or M6620) is a promising small-molecule ATR inhibitor that shows potential as an effective anticancer drug, both as monotherapy and in combination with chemotherapy or radiotherapy strategies, based on preclinical data and ongoing phase I/II clinical trials. [Read the Full Post]

Selective inhibition of ATM-dependent double-strand break repair and checkpoint control synergistically enhances the efficacy of ATR inhibitors

97 | Sep 17 2023

Inhibition of ATR kinase and simultaneous suppression of ATM kinase synergistically enhance cancer cell death and show promise as a novel combination approach for cancer therapy. [Read the Full Post]

Chemical inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4+ helper and CD8+ effector T cells

94 | Aug 31 2023

Inhibition of DNA-PKcs using small-molecule inhibitors abrogates T cell activation, impairs metabolic pathways and proliferation, and reduces cytotoxicity, highlighting its potential as a therapeutic target for immune modulation in autoimmune diseases, immune-related disorders, and cancer. [Read the Full Post]

PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis

60 | Aug 26 2023

The study identified multidrug-resistant CLL cells in patients and demonstrated that a small molecule activator of PP2A called DT-061 induced apoptosis in these cells independently of Bax/Bak, providing a potential strategy to overcome treatment resistance. [Read the Full Post]

Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3Kα

30 | Aug 20 2023

Researchers have developed a series of benzoxazepin-oxazolidinone ATP-competitive inhibitors, including GDC-0077 (inavolisib), which selectively target and degrade mutant p110α protein, a catalytic subunit of PI3Kα, demonstrating potential for the treatment of PIK3CA-mutant breast cancer in a Phase III clinical trial. [Read the Full Post]

Preclinical validation of a novel therapeutic strategy for choroid plexus carcinoma

103 | Aug 19 2023

This study represents a pioneering effort in identifying promising combinatorial therapeutics and highlighting the potential of intra-arterial delivery for the treatment of choroid plexus carcinoma, a rare and aggressive brain tumor in children. [Read the Full Post]

Nuclear pCHK1 as a potential biomarker of increased sensitivity to ATR inhibition

52 | Aug 19 2023

The study suggests that the nuclear-specific enrichment of checkpoint kinase 1 (CHK1) and higher levels of nuclear phosphorylated CHK1 (pCHK1) staining may serve as potential predictive biomarkers for sensitivity to the ATR inhibitor elimusertib in cancer cells. [Read the Full Post]

[Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR pathway-mediated autophagy]

26 | Aug 18 2023

Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR signaling-mediated autophagy in cardiomyocytes. [Read the Full Post]

Development and clinical application of a liquid chromatography-tandem mass spectrometry-based assay to quantify eight tyrosine kinase inhibitors in human plasma

27 | Aug 18 2023

This study successfully developed and validated a sensitive LC-MS/MS assay for the quantification of eight tyrosine kinase inhibitors in human plasma, demonstrating its potential clinical utility in therapeutic drug monitoring. [Read the Full Post]

Development of a colloidal gold immunochromatographic strip with enhanced signal for the detection of bovine parvovirus

47 | Aug 17 2023

The study successfully developed a signal-enhanced GICG strip with high sensitivity and specificity for detecting Bovine Parvovirus (BPV), making it a promising rapid and convenient diagnostic tool for BPV infection in the field. [Read the Full Post]

The Host Protein CAD Regulates the Replication of FMDV through the Function of Pyrimidines' De Novo Synthesis

77 | Aug 17 2023

This study elucidates the role of HDAC1 and the AKT-mTOR signaling pathway in promoting FMDV replication, while also highlighting the importance of the CAD ACTase domain and de novo pyrimidine synthesis, providing potential targets for the development of drugs against Foot-and-mouth disease virus. [Read the Full Post]

Targeting DNA Repair with Combined Inhibition of NHEJ and MMEJ Induces Synthetic Lethality in TP53-Mutant Cancers

38 | Aug 12 2023

Combining the DNA-PK/NHEJ inhibitor peposertib with the POLθ/MMEJ inhibitor novobiocin provides a rational treatment strategy for TP53-mutant solid tumors, resulting in synthetic lethality and potential therapeutic efficacy. [Read the Full Post]

Synergistic Targeting of DNA-PK and KIT Signaling Pathways in KIT Mutant Acute Myeloid Leukemia

32 | Aug 12 2023

This study demonstrates that targeting DNA-PK in KIT mutant acute myeloid leukemia (AML) cells, in combination with inhibitors of KIT signaling, shows synergistic effects and holds promise as a therapeutic strategy for this aggressive form of AML. [Read the Full Post]

Targeting VPS34 in autophagy: An update on pharmacological small-molecule compounds

20 | Aug 04 2023

This review summarizes the molecular structure, functions, and associations of VPS34 with human diseases, while also discussing the potential of small molecule inhibitors targeting VPS34 for future targeted drug development. [Read the Full Post]

Antiparasitic Activity of Plumbago auriculata Extracts and Its Naphthoquinone Plumbagin against Trypanosoma cruzi

30 | Aug 04 2023

The study demonstrates the potent antiparasitic activity of Plumbago auriculata crude extracts and its naphthoquinone Plumbagin against different forms and strains of Trypanosoma cruzi, suggesting their potential as promising alternatives for Chagas disease treatment. [Read the Full Post]

The effect of the ATM inhibitor AZD0156 on the radiosensitivity of human breast cancer and lung fibroblast cells

56 | Jul 31 2023

The combination of irradiation and AZD0156 showed enhanced efficacy in inducing cell cycle arrest and reducing clonogenic survival in breast cancer cells, while having minimal effect on fibroblast cells. [Read the Full Post]

Eganelisib, a First-in-Class PI3K-γ Inhibitor, in Patients with Advanced Solid Tumors: Results of the Phase 1/1b MARIO-1 Trial

18 | Jul 29 2023

The MAcrophage Reprogramming in Immuno-Oncology-1 (MARIO-1) study evaluated the safety and tolerability of eganelisib as a monotherapy and in combination with nivolumab in patients with solid tumors, with observed toxicities leading to the selection of eganelisib doses of 30 mg and 40 mg once daily for the phase 2 study. [Read the Full Post]

Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors

67 | Jul 28 2023

In this study, topical inhibition of the mTOR and/or PI3K pathways demonstrated promising results in increasing tumor-free survival and reducing squamous cell carcinoma in mice with anal dysplasia and anal cancer. [Read the Full Post]

Novel therapeutic approaches for pleural mesothelioma identified by functional ex vivo drug sensitivity testing

34 | Jul 28 2023

The study found that mTOR and Chk1 pathway inhibitors showed promising efficacy in established and patient-derived cell models of pleural mesothelioma, suggesting their potential as novel treatment strategies. [Read the Full Post]

A high-concentrate diet induces inflammatory injury via regulating Ca2+/CaMKKβ-mediated autophagy in mammary gland tissue of dairy cows

52 | Jul 26 2023

The study found that a high-concentrate diet induced autophagy in mammary gland tissue through the Ca2+/CaMKKβ-AMPK signaling pathway, leading to inflammatory injury in dairy cows. [Read the Full Post]

Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth

43 | Jul 22 2023

Tanshinone IIA (T2A), derived from the Chinese herb Danshen, inhibits cellular proliferation and reduces mTORC1 activity through increased expression of sestrin, suggesting its potential as a novel therapeutic agent for glioblastomas when used in combination with PI3K inhibitors. [Read the Full Post]

Multiparametric MR-PET Imaging Predicts Pharmacokinetics and Clinical Response to GDC-0084 in Patients with Recurrent High-Grade Glioma

25 | Jul 22 2023

Multiparametric MR-PET imaging utilizing composite biomarkers can effectively quantify the response to GDC-0084 treatment, estimate pharmacokinetic parameters, and predict progression-free survival in patients with recurrent malignant gliomas. [Read the Full Post]

Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes

50 | Jul 17 2023

This study demonstrates that centromere transcription in growing oocytes, associated with DNA repair proteins, plays a role in maintaining centromere stability and kinetochore assembly, providing insights into the accurate segregation of chromosomes during oocyte maturation. [Read the Full Post]

THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors

27 | Jul 14 2023

Combining the CDK12 inhibitor THZ531 with DNA repair inhibitors such as Olaparib holds potential as an effective therapeutic approach for multiple myeloma by inducing synergistic cell death and reducing tumor burden. [Read the Full Post]

Molecular insights into the behavior of the allosteric and ATP-competitive inhibitors in interaction with AKT1 protein: A molecular dynamics study

25 | Jul 12 2023

This computational study investigated the effects of various AKT1 inhibitors on the inactive and active conformations of the protein, revealing stable complexes and highlighting MK-2206 as having the strongest binding affinity in the inactive conformation and van der Waals interactions as the main contributors to binding energy. [Read the Full Post]

Apoptotic cell death in disease-Current understanding of the NCCD 2023

145 | Jul 09 2023

The Nomenclature Committee on Cell Death (NCCD) critically summarizes the extensive pre-clinical literature linking the core apoptotic apparatus to organismal homeostasis in various disease contexts, highlighting its role in both disease etiology and potential therapeutic interventions. [Read the Full Post]

FUT8-Mediated Core Fucosylation Promotes the Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

24 | Jul 08 2023

This study highlights the significant involvement of FUT8-mediated core fucosylation in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), suggesting FUT8 as a potential novel therapeutic target for PAH. [Read the Full Post]

Targeting transient receptor potential canonical 1 reduces non‑small cell lung cancer chemoresistance and stemness via inhibition of PI3K/AKT signaling

22 | Jul 03 2023

Targeting TRPC1 in non-small cell lung cancer (NSCLC) could reduce chemoresistance and cancer stemness by suppressing PI3K/Akt signaling, suggesting it as a potential therapeutic approach. [Read the Full Post]

Butyrate dictates ferroptosis sensitivity through FFAR2-mTOR signaling

36 | Jun 30 2023

Sodium butyrate enhances cell ferroptosis and inhibits tumor growth through downregulation of SLC7A11 and GPX4, mediated by the FFAR2-AKT-NRF2 and FFAR2-mTORC1 axes in a cAMP-PKA-dependent manner. [Read the Full Post]

Runx3-overexpression cooperates with ex vivo AKT inhibition to generate receptor-engineered T cells with better persistence, tumor-residency, and antitumor ability

110 | Jun 28 2023

Combining Runx3 overexpression with ex vivo AKT inhibition generates CAR-T cells with both tissue-resident and central memory characteristics, enhancing their persistence, cytotoxic potential, and tumor-residency ability for the treatment of solid tumors. [Read the Full Post]

Combination ATR (ceralasertib) and PARP (olaparib) Inhibitor (CAPRI) trial in acquired PARP-inhibitor-resistant homologous recombination deficient ovarian cancer

91 | Jun 23 2023

The combination of olaparib and ceralasertib shows promising activity and tolerability in patients with acquired PARPi-resistant high-grade serous ovarian cancer, suggesting the potential of ATRi to overcome PARPi resistance in this population. [Read the Full Post]

AZD8186 in Combination With Paclitaxel in Patients With Advanced Gastric Cancer: Results From a Phase Ib/II Study (KCSG ST18-20)

40 | Jun 23 2023

[Read the Full Post]

A Novel Tri-Functional Liposome Re-Educates "Cold Tumor" and Abrogates Tumor Growth by Synergizing Autophagy Inhibition and PD-L1 Blockade

45 | Jun 22 2023

This study demonstrates that a tri-functional liposomal system, DOX-SAR-JY4LIPO, combining doxorubicin, a VPS34 inhibitor, and an anti-PD-L1 peptide, effectively converts "cold tumors" into "hot tumors" by increasing immune cell infiltration and shows promise for improving cancer immunotherapy. [Read the Full Post]

Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical trials

0 | Jun 13 2023

Akt inhibitors show promise as a feasible and potentially effective approach for treating pediatric tumors by targeting the PI3K/Akt/mTOR signaling pathway. [Read the Full Post]

Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer

57 | Jun 12 2023

The study identified azeliragon as a potent inhibitor of PAK1 and demonstrated its ability to promote apoptosis in pancreatic cancer cells, inhibit tumor growth in a xenograft model, and exhibit a synergistic effect when combined with afuresertib, suggesting its potential as a novel treatment strategy for pancreatic cancer. [Read the Full Post]

Inhibition of GSK-3β Enhances Osteoblast Differentiation of Human Mesenchymal Stem Cells through Wnt Signalling Overexpressing Runx2

32 | May 29 2023

The study demonstrates that 1-Azakenpaullone, a highly selective inhibitor of GSK-3β, effectively induces osteoblastic differentiation and mineralization of human MSCs mediated by the activation of Wnt signaling and upregulation of Runx2, making it a promising osteo-promotor factor for bone tissue engineering. [Read the Full Post]

Maternal embryonic leucine zipper kinase in tumor cells and tumor microenvironment: An emerging player and promising therapeutic opportunity

12 | May 26 2023

MELK is a potential molecular target for cancer therapy due to its role in regulating tumor cell survival, growth, invasion, migration, and the tumor microenvironment, and small molecule inhibitors targeting it have shown promising results in clinical trials. [Read the Full Post]

Combining radiation and the ATR inhibitor berzosertib activates STING signaling and enhances immunotherapy via inhibiting SHP1 function in colorectal cancer

23 | May 22 2023

This study found that combining ATR inhibitors, irradiation, and anti-PD-L1 therapy improved the efficacy of immunotherapy in colorectal cancer mouse models by promoting STING signaling and reinvigorating the tumor microenvironment. [Read the Full Post]

MiR-139 Affects Radioresistance in Esophageal Cancer by Targeting the PDK1/AKT/Cyclin D1 Signaling Pathway

15 | May 21 2023

MiR-139 enhances radiosensitivity in esophageal cancer by regulating the cell cycle through the PDK1/Akt/Cyclin D1 signaling pathway, according to a study using KYSE150R cells and clinical data from 110 EC patients. [Read the Full Post]

Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation

35 | May 20 2023

Small molecule compounds promoting hepatocyte dedifferentiation may facilitate the growth of transplanted hepatocytes in vivo and improve the efficacy of hepatocyte therapy for end-stage liver disease. [Read the Full Post]

Recommendations on the use of azole antifungals in hematology-oncology patients

16 | May 19 2023

The administration of antifungal drugs in patients receiving hematology-oncology treatment requires careful monitoring and dose adjustments to minimize the risk of drug interactions and potential complications with certain antineoplastic drugs. [Read the Full Post]

Duvelisib Eliminates CLL B Cells, Impairs CLL-Supporting Cells, and Overcomes Ibrutinib Resistance in a Xenograft Model

18 | May 18 2023

The study demonstrates the essential roles of PI3K-δ and PI3K-γ in CLL and supports the use of duvelisib as a potential therapeutic intervention, including for patients who are resistant to BTKi therapy. [Read the Full Post]

A Cell System-Assisted Strategy for Evaluating the Natural Antioxidant-Induced Double-Stranded DNA Break (DSB) Style

98 | Apr 11 2023

Researchers evaluated whether natural antioxidants induce DNA damage using gene-knockout cell lines and found that sulforaphane induces single-strand breaks or DNA strand crosslinks, quercetin induces double-strand breaks, while resveratrol exerts cytotoxic effects other than DNA damage, and the mechanisms through which kaempferol and genistein induce DNA damage remain unknown. [Read the Full Post]

miR-223 Plays a Key Role in Obesogen-Enhanced Adipogenesis in Mesenchymal Stem Cells and in Transgenerational Obesity

68 | Apr 10 2023

The study found that exposure to the obesogen tributyltin (TBT) increased levels of the microRNA miR-223 in mesenchymal stem cells (MSCs), which may play a role in the development of obesity in male offspring of exposed pregnant mice through the PPARγ pathway. [Read the Full Post]

Design, synthesis and bioevaluation of 1,2,4-thiadiazolidine-3,5-dione derivatives as potential GSK-3β inhibitors for the treatment of Alzheimer's disease

116 | Apr 07 2023

The development of compound 10a as a potential GSK-3β inhibitor for Alzheimer's disease shows promising results in vitro and in vivo. [Read the Full Post]

Differential roles of phosphatidylinositol 3-kinase/akt pathway in retinal ganglion cell survival in rats with or without acute ocular hypertension

52 | Apr 03 2023

The study demonstrated that the PI3K/akt pathway is involved in mediating RGC survival following IOP elevation but not under normal conditions, suggesting its potential as a therapeutic target for ocular ischemic injuries and glaucoma. [Read the Full Post]

CUDC907, a dual phosphoinositide-3 kinase/histone deacetylase inhibitor, promotes apoptosis of NF2 Schwannoma cells

54 | Apr 03 2023

CUDC907, a dual HDAC/PI3K inhibitor, selectively reduces the viability of human merlin deficient Schwann cells (MD-SCs), promotes cell cycle arrest and caspase-3/7 activation, decreases levels of pAKT and YAP, and shows potential as a therapeutic option for Neurofibromatosis Type 2 (NF2). [Read the Full Post]

Co-targeting of HDAC, PI3K, and Bcl-2 results in metabolic and transcriptional reprogramming and decreased mitochondrial function in acute myeloid leukemia

49 | Apr 03 2023

The study found that the combination of CUDC-907 and venetoclax induces metabolic and transcriptomic reprogramming and suppresses oxidative phosphorylation in AML cells, providing a promising therapeutic approach for AML. [Read the Full Post]

ATM-SPARK: A GFP phase separation-based activity reporter of ATM

87 | Apr 02 2023

ATM-SPARK is a novel method for visualizing and measuring the activity of the kinase ATM during DNA damage response, allowing for the spatiotemporal dynamics of ATM activity to be observed in living cells and enabling high-throughput screening of biological and small-molecule regulators. [Read the Full Post]

A High-Throughput Screening Platform Identifies Novel Combination Treatments for Malignant Peripheral Nerve Sheath Tumors

37 | Apr 02 2023

The study identified a synergistic combination of MK-1775 with Doxorubicin as a potentially effective pharmacologic option for the treatment of malignant peripheral nerve sheath tumors. [Read the Full Post]

CDH6 as a prognostic indicator and marker for chemotherapy in gliomas

49 | Apr 01 2023

The study suggests that CDH6 may act as a promising target for glioma therapy, based on its positive correlation with tumor grade, negative correlation with patient prognosis, and associations with cell-cell interactions, immune processes, and potential drug targets. [Read the Full Post]

Bicarbonate transporter SLC4A7 promotes EMT and metastasis of HNSCC by activating the PI3K/AKT/mTOR signaling pathway

87 | Mar 29 2023

The study identifies SLC4A7 as a potential therapeutic target in HNSCC due to its promotion of EMT and metastasis through the PI3K/AKT/mTOR signaling pathway. [Read the Full Post]

Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells

51 | Mar 29 2023

The study found that the dual PI3K/mTOR inhibitor GDC-0980 induces cytotoxicity and apoptosis in GBM cells and may be a potential candidate for anti-GBM therapy. [Read the Full Post]

Selective Eradication of Colon Cancer Cells Harboring PI3K and/or MAPK Pathway Mutations in 3D Culture by Combined PI3K/AKT/mTOR Pathway and MEK Inhibition

18 | Mar 27 2023

This study identified a combination of small molecular inhibitors targeting the PI3K/AKT/MTOR and MAPK pathways that led to profound tumor cell destruction in 3D cultures of colorectal cancer cells. [Read the Full Post]

Design and development of novel 1,2,3-triazole chalcone derivatives as potential anti-osteosarcoma agents via inhibition of PI3K/Akt/mTOR signalling pathway

12 | Mar 27 2023

The manuscript describes the development of a novel series of 1,2,3-triazole chalcone derivatives as potential agents against osteosarcoma, which demonstrated significant inhibitory activity against PI3K and mTOR kinases, as well as promising anti-cancer activity in vitro against several cancer cell lines including OS. [Read the Full Post]

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study

139 | Mar 22 2023

This study identified the metabolomic profile and potential therapeutic effects of quercetin and its metabolites in cognitive impairment and Parkinson's disease, but further research is needed to confirm these findings in vivo and address potential adverse effects. [Read the Full Post]

Managing Vibration Training Safety by Using Knee Flexion Angle and Rating Perceived Exertion

118 | Mar 22 2023

This study found that a knee flexion angle of approximately 110 degrees is most effective in reducing vibration transmissibility during whole-body vibration exercise, while also observing a positive correlation between the rating of perceived exertion and the platform-to-head transmissibility. [Read the Full Post]

Defining the role of mTOR pathway in the regulation of stem cells of glioblastoma

49 | Mar 19 2023

Inhibition of the mTOR pathway, particularly with the small molecule inhibitor Torin2, shows potential as a strategy for targeting the cancer stem cells of glioblastoma, a deadly brain tumor characterized by resistance to conventional therapies. [Read the Full Post]

PI3Kδ inhibition potentiates glucocorticoids in B-ALL by decreased receptor phosphorylation and enhanced gene regulation

64 | Mar 19 2023

The research shows that combining a PI3Kδ inhibitor with glucocorticoids enhances the effectiveness of glucocorticoid therapy in B-lymphoblastic leukemia by decreasing inhibitory GR phosphorylation and enhancing downstream gene regulation. [Read the Full Post]

Targeting peripheral immune organs with self-assembling prodrug nanoparticles ameliorates allogeneic heart transplant rejection

72 | Mar 18 2023

The passage describes the development of a self-assembling nanoparticle, DHA-PP242 nanoparticle (DPNP), which targets immune organs to regulate T cell function and has shown promise in reducing inflammatory response and extending the survival of grafts in an experimental model of heart transplantation. [Read the Full Post]

Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health

66 | Mar 09 2023

Enhancing oligodendrocyte activity with the pharmaceutical drug Clemastine can prevent the chronic decline of microelectrode recording performance and improve the integration of functional device interfaces with brain tissue over a long period of time. [Read the Full Post]

Pharmacological treatment promoting remyelination enhances motor function after internal capsule demyelination in mice

57 | Mar 09 2023

This study suggests that the lysophosphatidylcholine-induced IC demyelination mouse model is useful for evaluating the effects of pharmacological treatments that promote remyelination on motor function and histological changes. [Read the Full Post]

The successful treatment of Enterocytozoon bieneusi Microsporidiosis with nitazoxanide in a patient with B-ALL: A Case Report

46 | Mar 01 2023

This case highlights the need to consider opportunistic infections in immunocompromised patients and the importance of using metagenomic sequencing in diagnosing such infections, as well as the limited available options for treating E. bieneusi infections and the need for further research. [Read the Full Post]

Addition of Nitazoxanide to Standard Clarithromycin Based Triple Therapy for 2 Weeks Effectively Eradicates Treatment-Naive Helicobacter Pylori Infection. A Single Centre prospective, open-label study

93 | Mar 01 2023

The NACE regimen (nitazoxanide, amoxicillin, clarithromycin, and esomeprazole) was found to be an effective and well-tolerated treatment for H. pylori infection, resulting in eradication in over 90% of patients in both per-protocol and intention to treat analyses. [Read the Full Post]

Pregabalin Mediates Retinal Ganglion Cell Survival From Retinal Ischemia/Reperfusion Injury Via the Akt/GSK3β/β-Catenin Signaling Pathway

47 | Feb 26 2023

Pregabalin protects retinal ganglion cells from ischemia/reperfusion injury-induced apoptosis by upregulating the Akt/GSK3β/β-catenin pathway. [Read the Full Post]

Integrative genomic analysis facilitates precision strategies for glioblastoma treatment

52 | Feb 24 2023

An integrative genomic analysis was conducted to advance individual-based therapies for Glioblastoma (GBM) by establishing a multiomics-based GBM classification, identifying subclass-specific efficacy of drugs, and developing a robust GBM poor prognostic signature score model that could be considered as potential biomarkers for immunotherapy response. [Read the Full Post]

Voxtalisib and low intensity pulsed ultrasound combinatorial effect on glioblastoma multiforme cancer stem cells via PI3K/AKT/mTOR

19 | Feb 24 2023

The study found that the combination of the dual inhibitor Voxtalisib (Vox) and low intensity pulsed ultrasound (LIPUS) effectively targeted Glioblastoma (GBM) and GBMCSCs by suppressing the PI3K/AKT/mTOR pathway, reducing cell viability and motility, and increasing autophagy, providing insight into a potential therapeutic approach for GBM. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

201 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

102 | Feb 18 2023

Rigosertib, a dual PLK1 and PI3K inhibitor, showed dose- and time-dependent efficacy against 5 human tumor cell lines in vitro, with A549 cells being the most sensitive and U87-MG cells the most resistant, with p53 levels affecting the efficacy, making Rigosertib a potential antineoplastic agent against lung cancer in humans. [Read the Full Post]

PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation

83 | Feb 18 2023

Rigosertib, an anticancer agent under clinical trials, targets PLK1 and modulates ELAVL1/HuR-miR-122 signaling to effectively inhibit the proliferation of wild-type and sofosbuvir resistance-associated HCVs, suggesting it could be useful for treating HCV and HCV-associated diseases. [Read the Full Post]

Lithium affects the circadian clock in the choroid plexus - A new role for an old mechanism

38 | Feb 14 2023

Lithium affects the circadian clock in the choroid plexus of the ventricle barrier complex, influencing brain function and potentially improving it in psychiatric patients by aligning the clock with the sleep-wake cycle, with potential for personalized timing of treatment. [Read the Full Post]

[Single-center study of different treatment for advanced or unresectable angiosarcoma patients]

125 | Feb 06 2023

This study found that doxorubicin-based and paclitaxel-based chemotherapy are the most common treatments for advanced angiosarcoma, and combined targeted therapy with anti-PD-1 immunotherapy showed potential efficacy in some patients with long duration of response and moderate adverse events. [Read the Full Post]

Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia

54 | Feb 02 2023

Platelet p110β dysfunction, caused by deficiency or inhibition, exacerbates pulmonary infection by impeding leukocyte functions, diminishing their infiltration and enhancing bacterial dissemination, thereby providing important insights into the immunomodulatory potential of PI3K inhibitors in bacterial infection. [Read the Full Post]

Inhibition of androgen receptor enhanced the anticancer effects of everolimus through targeting glucose transporter 12

37 | Jan 23 2023

Bo Cao et al. thought that interference with AR/GLUT12 pathway might serve as a promising approach to promoting the translational application of everolimus in GC therapy. [Read the Full Post]

Phenolipid JE improves metabolic profile and inhibits gluconeogenesis via modulating AKT-mediated insulin signaling in STZ-induced diabetic mice

50 | Jan 22 2023

Guihua Wang et al. suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway. [Read the Full Post]

Upregulation of glutamate transporter 1 by mTOR/Akt pathway in astrocyte culture during oxygen-glucose deprivation and reoxygenation

29 | Jan 21 2023

Mi Li et al. suggested that astrocytes might adapt to short-term ischemic-reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation. [Read the Full Post]

Interactive webtool for analyzing drug sensitivity and resistance associated with genetic signatures of cancer cell lines

124 | Jan 19 2023

Myriam Boeschen et al. found support for the described sensitivity of H1047 mutants to GSK690693 targeting the AKT pathway. [Read the Full Post]

A simple protein histidine kinase activity assay for high-throughput inhibitor screening

72 | Jan 16 2023

Donghee Lee et al. identified OSU-03012, a potent VanS HK inhibitor, which sensitized VRE toward vancomycin, highlighting the potential of AUDECY in HK inhibitor discovery. [Read the Full Post]

Combined femoral and acetabular version is sex-related and differs between patients with hip dysplasia and acetabular retroversion

23 | Jan 16 2023

Malin K Meier et al. found that patients with DDH and AR had remarkable sex-related differences of FV and CV. [Read the Full Post]

ATM deficiency aggravates the progression of liver fibrosis induced by carbon tetrachloride in mice

28 | Jan 13 2023

Ming Li et al. found that ATM might be a critical regulator of liver fibrosis progression. [Read the Full Post]

GSK3 inhibitor suppresses cell growth and metabolic process in FLT3-ITD leukemia cells

36 | Jan 11 2023

Jing Xia et al. suggested that BIO might be a promising therapeutic candidate for AML. [Read the Full Post]

PIK-24 Inhibits RSV-Induced Syncytium Formation via Direct Interaction with the p85α Subunit of PI3K

40 | Jan 03 2023

Li-Feng Chen et al. showed that a novel PI3K inhibitor inhibited RSV-induced PI3K signaling activation and actin cytoskeleton reorganization by targeting the p85α protein. [Read the Full Post]

Identification of Potential Treatments for Acute Lymphoblastic Leukemia through Integrated Genomic Network Analysis

23 | Jan 03 2023

Zulfan Zazuli et al. thought that chlorprothixene, sirolimus, dihydroergocristine, papaverine, and tamoxifen were the top five drug repositioning candidates for ALL according to the CMap score with dasatinib as a comparator. [Read the Full Post]

Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells

17 | Jan 02 2023

Barbora Adamová et al. thought that the combined therapy of perifosine and ABT-737 could be considered as a potential treatment strategy for colon cancer. [Read the Full Post]

Akt Pathway Inhibitors

70 | Jan 02 2023

Nne E Uko et al. suggested a mechanistic basis involving hyperactivated Akt signaling. Allosteric inhibitors were known to alter the activity of kinases. [Read the Full Post]

Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients

75 | Dec 31 2022

Karen E Anderson et al. explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients. [Read the Full Post]

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy

93 | Dec 30 2022

Massimo Breccia et al. suggested that further efforts were needed to improve the therapeutic management of later lines of CML. [Read the Full Post]

Rational Design and Synthesis of D-galactosyl Lysophospholipids as Selective Substrates and non-ATP-competitive Inhibitors of Phosphatidylinositol Phosphate Kinases

20 | Dec 16 2022

Mengxia Sun et al. thought that D-galactose-based phosphoinositide mimetics could be developed into artificial substrates and new inhibitors of PIPKs. [Read the Full Post]

Apilimod enhances specific productivity in recombinant CHO cells through cell cycle arrest and mediation of autophagy

20 | Dec 15 2022

Jiang-Tao Lu et al. found the potential of apilimod for development as a novel enhancer for the production of recombinant proteins in CHO cell engineering. [Read the Full Post]

Role of the Glycogen Synthase Kinase 3-Cyclic AMP/Protein Kinase A in the Immobilization of Human Sperm by Tideglusib

46 | Nov 21 2022

Weiwei Wang et al. found the GSK3-cAMP/PKA regulatory loop in human sperm, which might mediate the immobilization effect of tideglusib at low of concentrations (e.g., 1.25 μM) on sperm motility. [Read the Full Post]

PI3Kγ controls IL-17A expression and attenuates alveolar bone loss in an experimental periodontitis model

24 | Nov 17 2022

Marcelo Franchin et al. thought that PI3Kγ played an important role in modulating IL-17A expression and alveolar bone loss in vivo. [Read the Full Post]

AMPK-driven Macrophage Responses are Autophagy-dependent in Experimental Bronchopulmonary Dysplasia

41 | Nov 03 2022

Sourabh Soni et al. found that pharmacologic activation of AMPK by AICAR resulted in induction of autophagy and played a protective role. [Read the Full Post]

Acadesine alleviates acute pancreatitis-related lung injury by mediating the barrier protective function of pulmonary microvascular endothelial cells

30 | Nov 03 2022

Xiandong Zhu et al. found that acadesine attenuated SAP-ALI associated inflammation and tissue damage by modulating the Nrf2-dependent antioxidant pathway by triggering AMPK. [Read the Full Post]

Inhibiting PP2A Upregulates B7-H3 Expression and Potentially Increases the Sensitivity of Malignant Meningiomas to Immunotherapy by Proteomics

46 | Nov 02 2022

Boyi Hu et al. found that the PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy. [Read the Full Post]

ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer

67 | Oct 31 2022

S Lindsey Davis et al. found that AZD0156 and irinotecan provided a rational and active combination in preclinical colorectal cancer models. [Read the Full Post]

Combined ataxia telangiectasia mutated and DNA-dependent protein kinase inhibition radiosensitizes Madin-Darby canine kidney cells

29 | Oct 30 2022

Manabu Koike et al. suggested that MDCK cells might be useful in clarifying the cytotoxicity in canine epithelial cells due to radiation and/or radiosensitizers, such as molecule-targeted drugs. [Read the Full Post]

Randomized Phase II Trial of Sapanisertib ± TAK-117 vs. Everolimus in Patients With Advanced Renal Cell Carcinoma After VEGF-Targeted Therapy

49 | Oct 14 2022

Toni Choueiri et al thought that dual mTORC1/2 inhibition might not be an effective therapeutic approach for patients. [Read the Full Post]

Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver

21 | Oct 13 2022

Wenshu Tang et al. found mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment, providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic. [Read the Full Post]

Temsirolimus Enhances Anti-Cancer Immunity by Inducing Autophagy-Mediated Degradation of the Secretion of Small Extracellular Vesicle PD-L1

110 | Sep 29 2022

Seong-Sik Park et al. suggested that TEM, previously known as a targeted anti-cancer drug, could overcome the low reactivity of ICBT by inhibiting sEV PD-L1 and cellular PD-L1 levels. [Read the Full Post]

Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical trials

54 | Sep 29 2022

Bruno Toson et al. demonstrated the impact that Akt inhibition provided in tumorigenesis, and suggested targeting the PI3K/Akt/mTOR signaling pathway, alone or in combination with other inhibitors, was a feasible tool to achieve better outcomes in pediatric tumors. [Read the Full Post]

In silico drug repurposing and lipid bilayer molecular dynamics puzzled out potential breast cancer resistance protein (BCRP/ABCG2) inhibitors

66 | Sep 28 2022

Nahlah Makki Almansour et al. identified zotarolimus, temsirolimus and glecaprevir as auspicious anti-MDR drug leads that warrant further experimental assays. [Read the Full Post]

Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy

29 | Sep 18 2022

Santu Saha et al. found that while all inhibitors investigated might increase the efficacy of CRT, the greatest clinical potential of rucaparib might be in limiting kidney damage, which was dose-limiting. [Read the Full Post]

Dibutyl phthalate promotes angiogenesis in EA.hy926 cells through estrogen receptor-dependent activation of ERK1/2, PI3K-Akt, and NO signaling pathways

56 | Sep 15 2022

Dunja Kokai et al. found that DBP exerted a pro-angiogenic effect on human vascular ECs and described the molecular mechanism involving ER- and GPER-dependent activation of ERK1/2, PI3K-Akt, and NO signaling pathways. [Read the Full Post]

Co-inhibition of ATM and ROCK synergistically improves cell proliferation in replicative senescence by activating FOXM1 and E2F1

32 | Sep 14 2022

Eun Jae Yang et al. demonstrated a FOXM1- and E2F1-mediated molecular pathway enhancing cell cycle progression in cells with proliferative potential under replicative senescence conditions. [Read the Full Post]

Target of rapamycin (TOR) regulates the response to low nitrogen stress via autophagy and hormone pathways in Malus hupehensis

27 | Sep 11 2022

Danyang Li et al. found that appropriate inhibition of TOR activated autophagy and jasmonic acid signaling in M. hupehensis, which allowed plants to cope with low N stress. [Read the Full Post]

Unraveling the therapeutic potential of GANT61/Dactolisib combination as a novel prostate cancer modality

104 | Sep 08 2022

Mohamed Youssef et al. discovered that Dactolisib/GANT61 combination was promising in PCa treatment. [Read the Full Post]

BEZ235 Prolongs Murine Cardiac Allograft Survival Through the Autophagy Pathway

73 | Sep 08 2022

Xiaolong Miao et al. proposed a theoretical foundation for the strong connection between mTOR-induced autophagy and heart transplant. [Read the Full Post]

The PI3K/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis

0 | Sep 01 2022

Yangjiong Xiao et al. concluded that GSK458 might serve as an attractive candidate to treat ovarian cancer. [Read the Full Post]

PI3K/mTOR inhibitor omipalisib prolongs cardiac repolarization along with a mild proarrhythmic outcome in the AV block dog model

66 | Aug 31 2022

J J A van Bavel et al. found that chronic treatment of PI3K/mTOR inhibitor omipalisib prolonged the QT interval in a preclinical model under standardized proarrhythmic conditions. [Read the Full Post]

AKT phosphorylation as a predictive biomarker for PI3K/mTOR dual inhibition-induced proteolytic cleavage of mTOR companion proteins in small cell lung cancer

19 | Aug 31 2022

Ming-Chun Hung et al. suggested the level of p-AKT could be a companion diagnostic biomarker for the treatment of SCLC involving the combinational use of clinically approved isoform-specific PI3K and mTOR inhibitors. [Read the Full Post]

Chronic AMPK Activation Reduces the Expression and Alters Distribution of Synaptic Proteins in Neuronal SH-SY5Y Cells

28 | Aug 29 2022

Alex J T Yang et al. suggested that chronic AMPK activation impacted synaptic protein content and reduced neurite protein abundance and distribution. [Read the Full Post]

Chloroquine-Induced DNA Damage Synergizes with Nonhomologous End Joining Inhibition to Cause Ovarian Cancer Cell Cytotoxicity

54 | Aug 11 2022

María Ovejero-Sánchez et al. found that NHEJ inhibition increased the persistence of γH2AX foci after CQ-induced DNA damage, revealing an essential role of this pathway in the repair of the lesions. [Read the Full Post]

Therapeutic targeting of TANK-binding kinase signaling towards anticancer drug development: Challenges and opportunities

62 | Aug 10 2022

Manzar Alam et al. highlighted the therapeutic potential of potent and selective TBK1 inhibitors, including Amlexanox, Compound II, BX795, MRT67307, SR8185 AZ13102909, CYT387, GSK8612, BAY985, and Domainex. [Read the Full Post]

Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles

62 | Aug 10 2022

Roshni Iyer et al. found that E-DSNPs displayed very high uptake by lung cancer cells compared to healthy lung epithelial cells. [Read the Full Post]

Alpelisib combination treatment as novel targeted therapy against hepatocellular carcinoma

76 | Aug 05 2022

Hongwei Xu et al. demonstrated that alpelisib was effective for treating PIK3CA-mutated HCC by inhibiting MAPK and AKT cascades. [Read the Full Post]

Comprehensive genome profiling in patients with metastatic non-small cell lung cancer: the precision medicine phase 2 randomized SAFIR02-Lung trial

52 | Aug 01 2022

Fabrice Barlesi et al. thought that molecular profiling could feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC. [Read the Full Post]

mTORC1 and mTORC2 Complexes Regulate the Untargeted Metabolomics and Amino Acid Metabolites Profile through Mitochondrial Bioenergetic Functions in Pancreatic Beta Cells

62 | Jul 30 2022

Ghada A Soliman et al. thought that third-generation mTOR inhibitors might alter the mitochondrial dynamics and reveal a bioenergetics profile that could be targeted to reduce mitochondrial stress. [Read the Full Post]

BKM120 alters the migration of doublecortin-positive cells in the dentate gyrus of mice

36 | Jul 28 2022

Yeonggwang Hwang et al. suggested that the altered migration of adult-born neurons in the dentate gyrus played a role in mood disturbances. [Read the Full Post]

Patient-derived models of brain metastases recapitulate human disseminated disease

31 | Jul 27 2022

Claudia C Faria et al. thought that models of BMs recapitulated the biology of human metastatic disease and could be valuable translational platforms for precision medicine. [Read the Full Post]

Inhibiting PI3K-AKT-mTOR Signaling in Multiple Myeloma-Associated Mesenchymal Stem Cells Impedes the Proliferation of Multiple Myeloma Cells

97 | Jul 25 2022

Luca Heinemann et al. found that targeting PI3K-AKT-mTOR signaling in MSCs might represent an additional therapeutic pathway in the treatment of MM patients. [Read the Full Post]

GDC-0941 activates integrin linked kinase (ILK) expression to cause resistance to GDC-0941 in breast cancer by the tumor necrosis factor (TNF)-α signaling pathway

52 | Jul 25 2022

Haifeng Chen et al. thought that GDC-0941 increased ILK level by upregulating TNF-α, thus affecting AKT expression and the sensitivity of breast cancer cells to GDC-0941. [Read the Full Post]

AMPK-ChREBP axis mediates de novo milk fatty acid synthesis promoted by glucose in the mammary gland of lactating goats

84 | Jul 21 2022

Hengbo Shi et al. thought that glucose supplementation promoted de novo fatty acid synthesis via the AMPK-ChREBP axis, hence increasing milk fat yield in the goat mammary gland. [Read the Full Post]

Antifungal activity of dehydrocurvularin for Candida spp. through the inhibition of adhesion to human adenocarcinoma cells

85 | Jul 21 2022

Hitoshi Kamauchi et al. reported that dehydrocurvularin (1), isolated from the marine-derived fungus Curvularia aeria, exhibited anti-fungal activities for Candida albicans and Candida auris. [Read the Full Post]

Ipatasertib, an oral AKT inhibitor, inhibits cell proliferation and migration, and induces apoptosis in serous endometrial cancer

160 | Jul 12 2022

Lindsey Buckingham et al. found that IPAT significantly inhibited cell proliferation and colony formation in a dose-dependent manner in USC cells. [Read the Full Post]

The close interaction between hypoxia-related proteins and metastasis in pancarcinomas

160 | Jul 11 2022

Andrés López-Cortés et al. identified 23 drugs enrolled in clinical trials focused on metastatic disease treatment. [Read the Full Post]

Simultaneously targeting ErbB family kinases and PI3K in HPV-positive head and neck squamous cell carcinoma

45 | Jun 29 2022

Zejia Yang et al. found that Afatinib and Copanlisib more effectively suppressed cell proliferation and survival of HPV-positive HNSCC in comparison to either treatment alone. [Read the Full Post]

Resistance to PI3κδ inhibitors in marginal zone lymphoma can be reverted by targeting the IL-6/PDGFRA axis

74 | Jun 29 2022

Alberto J Arribas et al. presented a model of secondary resistance to PI3Kffinhibitors obtained by prolonged exposure of a splenic MZL cell line to idelalisib. [Read the Full Post]

Prospects of targeting PI3K/AKT/mTOR pathway in pancreatic cancer

154 | Jun 27 2022

Motahareh Mortazavi et al. reported that whole-genome analyses demonstrated the frequent involvement of aberrant activations of PI3K/AKT/mTOR pathway components in PDAC patients. [Read the Full Post]

The Application of ATR Kinase Inhibitor AZD6738 in Combination with Radiotherapy for the Treatment of Melanoma

98 | Jun 24 2022

Maryam Talebpoor et al. provided insight into the impact of Ataxia Telangiectasia and Rad3-related kinase (ATR) inhibition on the potential role of this kinase in the suppression of melanoma cell proliferation. [Read the Full Post]

A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease

107 | Jun 24 2022

Geru Tao et al. found that inhalation of hydrogen/oxygen improved serum lipid and liver enzymes. [Read the Full Post]

Tenofovir alafenamide prophylaxis post-liver transplantation: a real-world study in patients with chronic kidney disease

175 | Jun 19 2022

E Sinakos et al. found that conversion to TAF in post-LT patients who develop CKD did not lead to improvement of kidney function after a period of one year. [Read the Full Post]

ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway

367 | Jun 10 2022

Jufeng Sun et al. thought that ARHGAP9 inhibited the malignant phenotypes of CRC cells via interdicting PI3K/AKT/mTOR signaling pathway. [Read the Full Post]

Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells

97 | May 30 2022

Manuela Piazzi et al. indicated that BYL-719, either alone or in combination with the p110δ inhibitor, CAL-101, could represent an efficient treatment for human rhabdomyosarcoma presenting with aberrant upregulation of the PI3K signaling pathway. [Read the Full Post]

Palbociclib-based high-throughput combination drug screening identifies synergistic therapeutic options in HPV-negative head and neck squamous cell carcinoma

113 | May 29 2022

Ziyue Gu et al. provided insights into the systematic combinatory effect associated with CDK4/6 inhibition and supported further initiation of clinical trials using the palbociclib plus alpelisib combination in HPVneg HNSCC with PIK3CA alterations. [Read the Full Post]

Evaluation of mitochondrial oxidative toxicity in mammalian cardiomyocytes by determining the highly reproducible and reliable increase in mitochondrial superoxides after exposure to therapeutic drugs

278 | May 27 2022

Dohee Ahn et al. found that a screening system using MitoSOX™ had the potential to be applied as a reliable biomarker for determining mitochondrial oxidative toxicity in new drug development. [Read the Full Post]

Vasorelaxant effect of curcubisabolanin A isolated from Curcuma longa through the PI3K/Akt/eNOS signaling pathway

186 | May 25 2022

Jin-Feng Chen et al. demonstrated that the vasorelaxant effect of curcubisabolanin A was partially endothelium-dependent. [Read the Full Post]

Intron retention coupled with nonsense-mediated decay is involved in cellulase biosynthesis in cellulolytic fungi

200 | May 20 2022

Yichen Gao et al. provided better understanding on intron retention, the NMD pathway, and cellulase production mechanism in filamentous fungi. [Read the Full Post]

Premise and peril of Wnt signaling activation through GSK-3β inhibition

216 | May 19 2022

Samuel M Law et al. thought that caution was required when micromolar levels of CHIR-99021 were used for the purpose of activating the canonical Wnt signaling pathway. [Read the Full Post]

Impact of optimal vaccination and social distancing on COVID-19 pandemic

231 | May 10 2022

Sangeeta Saha et al. observed that maintaining physical distancing and taking vaccines at an early stage decreases the infection level significantly in the environment by reducing the probability of becoming infected. [Read the Full Post]

Microangiopathy associated with gemcitabine: a drug interaction with nab-paclitaxel? A case series and literature review

141 | May 05 2022

Jeanne Allard et al. thought high incidence rate of G-TMA was observed in the cohort due to a potential drug interaction between nab-paclitaxel and gemcitabine with an increased risk of developing G-TMA. [Read the Full Post]

Long non-coding RNA ATXN8OS Promotes Ferroptosis and Inhibits the Temozolomide-resistance of Gliomas Through the ADAR/GLS2 Pathway

270 | Apr 26 2022

Jin Luo et al. found that ATXN8OS mediated ferroptosis and regulated the TMZ-resistance of glioma via ADAR/GLS2 pathway. [Read the Full Post]

Clinically relevant CHK1 inhibitors abrogate wild-type and Y537S mutant ERα expression and proliferation in luminal primary and metastatic breast cancer cells

437 | Apr 20 2022

Sara Pescatori et al. thought that CHK1 could be considered as an appealing novel pharmacological target for the treatment of luminal primary and MBCs. [Read the Full Post]

In Vitro Evaluation of Rigosertib Antitumoral and Radiosensitizing Effects against Human Cholangiocarcinoma Cells

416 | Apr 01 2022

Alessio Malacrida et al. thought that rigosertib could be a potential therapeutic option, alone or in combination with radiations, for nonresectable patients with cholangiocarcinoma. [Read the Full Post]

Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair

353 | Mar 31 2022

Alessio Malacrida et al. hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. [Read the Full Post]

DNA repair protein DNA-PK protects PC12 cells from oxidative stress-induced apoptosis involving AKT phosphorylation

235 | Mar 30 2022

Alessio Cardinale et al. found that DNA-PK could protect cells from oxidative stress induced-apoptosis independently from its function of DSB repair enzyme. [Read the Full Post]

A phase I study investigating AZD8186, a potent and selective inhibitor of PI3Kβ/δ, in patients with advanced solid tumors

117 | Mar 16 2022

Atish D Choudhury et al. showed preliminary evidence of limited anti-tumor activity by imaging and, in prostate cancer, PSA reduction. [Read the Full Post]

Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth

414 | Mar 07 2022

Rameswari Chilamakuri et al. found that the dual inhibition of PI3K and HDAC by CUDC-907 was an effective therapeutic strategy for NB and other MYC-dependent cancers. [Read the Full Post]

Unfolded protein response-induced expression of long noncoding RNA Ngrl1 supports peripheral axon regeneration by activating the PI3K-Akt pathway

164 | Mar 06 2022

Dong Wang found that unfolded protein response-induced Ngrl1 expression supports the intrinsic control of peripheral axon regeneration by modulating the activation of the PI3K-Akt pathway following SNC. [Read the Full Post]

Recent Advances of PI3 Kinase Inhibitors: Structure Anticancer Activity Relationship Studies

127 | Mar 03 2022

Vivek Asati et al. focused on the structural insights and structure anticancer activity relationship studies of recent PI3K inhibitors including their clinical stages of development and therapeutic values. [Read the Full Post]

GSK-3β manipulates ferroptosis sensitivity by dominating iron homeostasis

235 | Mar 03 2022

Lingjuan Wang et al. showed that the multifaceted Ser/Thr protein kinase GSK-3β acted as a positive modulator of the ferroptosis program. [Read the Full Post]

Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I

124 | Mar 02 2022

Ian E Krop et al. showed that taselisib monotherapy had very limited activity in a heterogeneous cohort of heavily pretreated cancer patients with PIK3CA-mutated tumors [Read the Full Post]

AMPK-PERK axis represses oxidative metabolism and enhances apoptotic priming of mitochondria in acute myeloid leukemia

177 | Feb 25 2022

Adrien Grenier et al. thought that selective AMPK-activating compounds kiledl AML cells by rewiring mitochondrial metabolism that primed mitochondria to apoptosis by BH3 mimetics, holding therapeutic promise in AML. [Read the Full Post]

Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells

478 | Feb 21 2022

Yadong Sun et al. thought that the combined application of ferroptosis inducers and mTOR inhibitors was a promising approach to improve therapeutic options in the treatment of bladder cancer. [Read the Full Post]

Pro-Inflammatory and Pro-Oxidative Changes During Nilotinib Treatment in CML Patients: Results of a Prospective Multicenter Front-Line TKIs Study (KIARO Study)

402 | Feb 20 2022

Anna Sicuranza et al. showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib. [Read the Full Post]

ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization

383 | Feb 18 2022

Tingting Qin et al. found that ATRX-deficient high-grade gliomas (HGGs) displayed Chk1-mediated dysregulation of cell-cycle phase transitions. [Read the Full Post]

The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells

0 | Feb 10 2022

Kamira Maharaj et al. suggested that the improved safety profile of umbralisib was due to its role as a dual PI3Kδ/CK1ε inhibitor that preserved Treg number and function. [Read the Full Post]

PI3Kδ/γ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity

150 | Feb 10 2022

Christopher Ronald Funk et al. found that exposure of CART to a PI3Kδ/γ inhibitor during manufacturing enriched the CART product for CD8+ CART cells with stem-like qualities and enhanced efficacy in eliminating CLL in vivo. [Read the Full Post]

Transcriptome Analysis of Cells Exposed to Actinomycin D and Nutlin-3a Reveals New Candidate p53-Target Genes and Indicates That CHIR-98014 Is an Important Inhibitor of p53 Activity

197 | Feb 01 2022

Barbara Łasut-Szyszka et al. thought that an unidentified kinase inhibited by CHIR-98014, participated in modification of p53 and enabled it to activate a subset of its target genes. [Read the Full Post]

hnRNP C modulates MERS-CoV and SARS-CoV-2 replication by governing the expression of a subset of circRNAs and cognitive mRNAs

167 | Jan 28 2022

Xi Zhang et al. identified hnRNP C as a key regulator of MERS-CoV-perturbed circRNAs and their cognate mRNAs. [Read the Full Post]

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

929 | Jan 27 2022

Xingyi Cheng et al. indicated that GSK690693 might become an effective compound for anti-aging intervention. [Read the Full Post]

Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation

240 | Jan 20 2022

Florence Choo et al. suggested that molecularly targeted strategies might be effective in PI3K/AKT/mTOR-activated ssRMS. [Read the Full Post]

Regulation of the mammalian maternal-to-embryonic transition by eukaryotic translation initiation factor 4E

544 | Jan 18 2022

Yan Li et al. thought that eIF4E activity was regulated at key embryonic transitions in the mammalian embryo and was essential for the successful transition from maternal to embryonic control of development. [Read the Full Post]

Differential time course of glycogen synthase kinase-3 inhibition in experimental autoimmune encephalomyelitis

349 | Dec 29 2021

A S Al-Zaidi et al. found that downregulation of Th1 and Th17 hallmark cytokines by Tideglusib in EAE might be associated with IL-10 production. [Read the Full Post]

Medium & long-chain acylcarnitine's relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study

353 | Dec 10 2021

Dan-Meng Zheng et al. found that C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine. [Read the Full Post]

Downregulation of AMPK dependent FOXO3 and TFEB involves in the inhibition of autophagy in diabetic cataract

414 | Dec 09 2021

Jiani Li et al. thought that targeting AMPK-induced autophagy might be a potential therapeutic approach for diabetic cataract. [Read the Full Post]

Activation of Yes-Associated Protein/PDZ-Binding Motif Pathway Contributes to Endothelial Dysfunction and Vascular Inflammation in AngiotensinII Hypertension

443 | Dec 08 2021

Qian Xu et al. suggested that AngII induced YAP/TAZ activation via PP2A-dependent dephosphorylation, which might contribute to the impairment of endothelial function and the induction of vascular inflammation in hypertension. [Read the Full Post]

MAD2B-mediated cell cycle reentry of podocytes is involved in the pathogenesis of FSGS

431 | Dec 06 2021

Dian Bao et al. found that ATM kinase-MAD2B axis importantly contributed to the cell cycle reentry of podocytes. [Read the Full Post]

Targeting the ATM Kinase to Enhance the Efficacy of Radiotherapy and Outcomes for Cancer Patients

402 | Dec 06 2021

María E Guerra García et al. suggest that ATM inhibitors might be particularly effective in tumors with defects in other nodes of the DNA damage response. [Read the Full Post]

First-in-child phase I/II study of the dual mTORC1/2 inhibitor vistusertib (AZD2014) as monotherapy and in combination with topotecan-temozolomide in children with advanced malignancies: arms E and F of the AcSé-ESMART trial

314 | Nov 19 2021

Raphael J Morscher et al. found that vistusertib was well tolerated in paediatric patients. [Read the Full Post]

Rapalogs induce non-apoptotic, autophagy-dependent cell death in HPV-negative TP53 mutant head and neck squamous cell carcinoma

369 | Nov 08 2021

Md Maksudul Alam et al. found that rapalogs promoted non-apoptotic ADCD in HPV-negative mutTP53 HNSCC via the ULK1 pathway. [Read the Full Post]

Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer

342 | Nov 08 2021

Shannon N Westin et al. found that the combination of olaparib and capivasertib was associated to no serious adverse events and demonstrated durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. [Read the Full Post]

The mTOR Inhibitor Temsirolimus Added to Rituximab Combined With Dexamethasone, Cytarabine, and Cisplatinum (R-DHAP) for the Treatment of Patients With Relapsed or Refractory DLBCL - Results From the Phase-II STORM Trial

327 | Nov 07 2021

Mathias Witzens-Harig et al. concluded that temsirolimus could be safely added to rituximab and DHAP with promising activity. [Read the Full Post]

Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells

332 | Oct 27 2021

Andrea Ghelli Luserna Di Rorà et al. found that the ATR-CHK1 pathway was involved in the response to Dox-induced DNA damage. [Read the Full Post]

Ceramide modulates electrophysiological characteristics and oxidative stress of pulmonary vein cardiomyocytes

758 | Oct 24 2021

Shih-Yu Huang et al. thought that C2 ceramide might exert the distinctive electrophysiological effect of modulating PV activities. [Read the Full Post]

AZD8055 ameliorates experimental autoimmune encephalomyelitis via the mTOR/ROS/NLRP3 pathway

440 | Oct 20 2021

Miao He et al. provided insights into the interactions between autophagy and pyroptosis and might facilitate the development of novel treatments for MS. [Read the Full Post]

Dual PI3K/mTOR inhibitor NVP‑BEZ235 decreases the proliferation of doxorubicin‑resistant K562 cells

1452 | Oct 17 2021

Jie Li et al. suggested that BEZ235 might reverse Doxo resistance in leukemia cells. [Read the Full Post]

Targeting mTOR signaling overcomes acquired resistance to combined BRAF and MEK inhibition in BRAF-mutant melanoma

743 | Oct 17 2021

Beike Wang et al. revealed that mTOR activation was essential for drug resistance of melanoma to MAPK inhibitors, and provided insight into the rewiring of the signaling networks in CR melanoma. [Read the Full Post]

rhKGF-2 Attenuates Smoke Inhalation Lung Injury of Rats via Activating PI3K/Akt/Nrf2 and Repressing FoxO1-NLRP3 Inflammasome

384 | Oct 10 2021

Zhonghua Fu et al. found that rhKGF-2 mitigated SILI by regulating the PI3K/Akt/Nrf2 pathway and the FoxO1-NLRP3 axis, which provided new reference in treating SILI. [Read the Full Post]

GSK2126458 has the potential to inhibit the proliferation of pancreatic cancer uncovered by bioinformatics analysis and pharmacological experiments

315 | Oct 09 2021

Yueqin Feng et al. found that the PI3K-Akt signaling pathway may be a key pathway for pancreatic cancer, our study uncovered the potential therapeutic potential of GSK2126458, a specific mTOR inhibitor, for pancreatic cancer. [Read the Full Post]

Structural basis of the selective activation of enzyme isoforms: Allosteric response to activators of β1- and β2-containing AMPK complexes

849 | Oct 06 2021

Elnaz Aledavood et al. found the design of activators tailored for improving the therapeutic treatment of tissue-specific metabolic disorders. [Read the Full Post]

Improvement of the LbCas12a-crRNA System for Efficient Gene Targeting in Tomato

614 | Sep 16 2021

Tien Van Vu et al. demonstrated the significance of the selection of gene scissors, the appropriate design and number of LbCas12a crRNAs, the use of chemical treatments. [Read the Full Post]

Prophylactic treatment with BX795 blocks activation of AKT and its downstream targets to protect vaginal keratinocytes and vaginal epithelium from HSV-2 infection

433 | Sep 15 2021

Krishnaraju Madavaraju et al. found that BX795 efficiently reduced phosphorylation of AKT and its downstream targets p70S6K and 4EBP1. [Read the Full Post]

mTOR inhibitor INK128 promotes wound healing by regulating MDSCs

217 | Sep 11 2021

Yi Li et al. found that INK128 is potential to be developed as a clinical strategy to promote wound healing of diabetic patients. [Read the Full Post]

Antitumor effects of AZD2014, a dual mTORC1/2 inhibitor, against human hepatocellular carcinoma xenograft in nude mice

463 | Sep 07 2021

H Liao et al. found that AZD2014 was a highly potent antitumor agent for HCC in nude mice bearing HCC xenografts. [Read the Full Post]

Oncogene-independent resistance in Philadelphia chromosome - positive (Ph +) acute lymphoblastic leukemia (ALL) is mediated by activation of AKT/mTOR pathway

250 | Sep 06 2021

Afsar Ali Mian et al. found that Torin-1 and NVP-BEZ235 induced apoptosis in PH and BV cells but not in HP cells. [Read the Full Post]

Tyrosine Kinase Inhibitors Stimulate HLA Class I Expression by Augmenting the IFNγ/STAT1 Signaling in Hepatocellular Carcinoma Cells

270 | Sep 02 2021

Aya Takahashi et al. found that regorafenib had an activating effect on signal transducers and activators of transcription 1 (STAT1), and that regorafenib-induced HLA-I expression was dependent on the augmented IFNγ/STAT1 signaling pathway. [Read the Full Post]

PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation

317 | Sep 02 2021

Rachel Y Chow et al. suggested that PI3K promoted BCC tumor growth by kinase-induced p21 degradation without altering HH signaling. [Read the Full Post]

High-Throughput Screening Identifies Ascorbyl Palmitate As a SIRT2 Deacetylase and Defatty-Acylase Inhibitor

445 | Aug 31 2021

Jun Young Hong et al. discovered novel SIRT2 deacylase inhibitors and presented a screening approach that could be applied on a larger scale. [Read the Full Post]

Abbreviated Profile of Drugs (APOD): modeling drug safety profiles to prioritize investigational COVID-19 treatments

453 | Aug 31 2021

Chaitanya N Hiremath found that drugs with strong safety profiles included molnupiravir (EIDD-2801), moderate safety profiles included dexamethasone, and weak safety profiles included lopinavir. [Read the Full Post]

Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport

755 | Aug 27 2021

Changhong Ren et al. suggested that supplemental activation of glucose transport after CCH might provide a clinically applicable intervention for improving cognitive impairment. [Read the Full Post]

ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins

420 | Aug 19 2021

Clara Alcon et al. found that the anti-apoptotic proteins BCL-xL and MCL-1 were crucial for ER+ breast cancer cells resistance to therapy. [Read the Full Post]

Pharmacokinetics of Ipatasertib in Subjects With Hepatic Impairment Using Two Methods of Classification of Hepatic Function

450 | Aug 18 2021

Rucha Sane et al. showed that no dosage adjustment was required for ipatasertib when treating patients with mild hepatic impairment, whereas a dose reduction would be recommended for subjects with moderate or severe hepatic impairment. [Read the Full Post]

Phase I trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

194 | Aug 05 2021

Grégoire Marret et al. found that copanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients. [Read the Full Post]

ASN007 is a selective ERK1/2 inhibitor with preferential activity against RAS-and RAF-mutant tumors

213 | Aug 04 2021

Ana Portelinha et al. found that the PI3K inhibitor copanlisib enhanced the antiproliferative activity of ASN007 both in vitro and in vivo due to dual inhibition of RAS/MAPK and PI3K survival pathways. [Read the Full Post]

Idelalisib immune-related toxicity is associated with improved treatment response

301 | Aug 03 2021

Nina D Wagner-Johnston et al. showed a trend correlating idelalisib-induced Grade ≥3 irAEs with improved efficacy. [Read the Full Post]

Hydrogen-Rich Medium Regulates Cr(VI)-Induced ER Stress and Autophagy Signaling in DF-1 Cells

432 | Aug 02 2021

Kangping Liu et al. found that HRM could protect cells from damage induced by Cr(VI), and played a role by inhibiting ER stress-mediated autophagy. [Read the Full Post]

Ceralasertib (AZD6738), an oral ATR kinase inhibitor, in combination with carboplatin in patients with advanced solid tumors: a Phase I study

435 | Aug 01 2021

Timothy A Yap et al. reported the safety, tolerability, maximum tolerated dose (MTD), recommended Phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile and preliminary antitumor activity of ceralasertib combined with carboplatin in patients with advanced solid tumors [Read the Full Post]

Pre-incubation with OATP1B1 and OATP1B3 inhibitors potentiates inhibitory effects in physiologically relevant sandwich-cultured primary human hepatocytes

623 | Jul 28 2021

Taleah Farasyn et al. thought that IC50 values after inhibitor-preincubation in transporter-expressing cell lines might be used for DDI prediction for the purpose of mitigating false-negative OATP-mediated DDI prediction. [Read the Full Post]

Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats

2624 | Jul 20 2021

Changju Hou et al. demonstrated that 11R‑VIVIT promoted fracture healing in osteoporotic rats and enhanced the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway. [Read the Full Post]

A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations

251 | Jul 11 2021

Guillaume Canaud et al. thought that management of patients with PIK3CA-related disorders required a multidisciplinary approach. [Read the Full Post]

Successful Treatment of a Locally Recurrent and Metastatic Malignant Phyllodes Tumor with Accelerated Radiotherapy and Nab-Paclitaxel, Cisplatin, and Liposomal Doxorubicin Chemotherapy

1157 | Jul 08 2021

Ioannis M Koukourakis et al. found that the combination of cisplatin with nab-paclitaxel and liposomal doxorubicin chemotherapy had acceptable toxicity and was highly effective in eradicating metastatic lesions. [Read the Full Post]

Diffuse optical tomography breast imaging measurements are modifiable with pre-surgical targeted and endocrine therapies among women with early stage breast cancer

507 | Jul 06 2021

Julia E McGuinness et al. demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy. [Read the Full Post]

Evolution of β-catenin-independent Wnt-GSK3-mTOR signalling in regulation of energy metabolism in isoproterenol-induced cardiotoxicity model

461 | Jun 30 2021

Shriyansh Srivastava et al. discussed a novel therapeutic role of the β-catenin independent, Wnt-GSK3-mTOR axis in attenuation of Iso-induced cardiotoxicity in rodents. [Read the Full Post]

GSK3ß inhibitor CHIR 99021 modulates cerebral organoid development through dose-dependent regulation of apoptosis, proliferation, differentiation and migration

664 | Jun 29 2021

Chloe Delepine et al. revealed new mechanisms of the pleiotropic effects of GSK3β during organoid development, providing essential information for the improvement of organoid production and ultimately shedding light on the mechanisms of embryonic brain development. [Read the Full Post]

Binding Insights into Quadruplex Selective Carbazole Ligands

534 | Jun 18 2021

Diana Müller et al. thought that carbazole was a very promising scaffold for assembling G4 ligands with a range of novel functional applications. [Read the Full Post]

A sulfobetaine zwitterionic polymer-drug conjugate for multivalent paclitaxel and gemcitabine co-delivery

294 | Jun 10 2021

Haotian Sun et al. thought that ZPDCs were promising systems for chemotherapy delivery and bioimaging applications. [Read the Full Post]

Vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma: First results of a multicenter, open-label, phase 2 trial (VISMONEO study): Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma

382 | Jun 03 2021

Nicolas Bertrand et al. found that Neoadjuvant vismodegib allowed for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations. [Read the Full Post]

Bintrafusp alfa (M7824), a bifunctional fusion protein targeting TGF-β and PD-L1: results from a phase I expansion cohort in patients with recurrent glioblastoma Mustafa Khasraw 1 2,

649 | Jun 01 2021

[Read the Full Post]

Treatment of Luminal Metastatic Breast Cancer beyond CDK4/6 Inhibition: Is There a Standard of Care in Clinical Practice?

1203 | May 21 2021

Athanasios Mavratzas et al. thought that treatment of metastatic luminal breast cancer after progression on CDK4/6 inhibitors remained a challenge. [Read the Full Post]

Therapeutic targeting PLK1 by ON-01910.Na is effective in local treatment of retinoblastoma

663 | Apr 21 2021

Huan Ma et al. demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. [Read the Full Post]

A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent

701 | Apr 21 2021

Stacey J Baker et al. found that these cells failed to proliferate in the presence of rigosertib at concentrations that are lethal to wild-type cells. [Read the Full Post]

Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer

433 | Apr 19 2021

Yang Zhou et al. demonstrated that IPO4 and CEBPD knockdown improved CDDP-induced cytotoxicity in vitro and in vivo. [Read the Full Post]

Isoform- and phosphorylation-specific multiplexed quantitative pharmacodynamics of drugs targeting PI3K and MAPK signaling in xenograft models and clinical biopsies

210 | Apr 01 2021

William G Herrick et al. demonstrated the degree and duration of phosphorylation modulation for three distinct classes of drugs targeting the PI3K/AKT and MAPK pathways. [Read the Full Post]

Targeting phosphoinositide 3-kinases and histone deacetylases in multiple myeloma

544 | Mar 19 2021

Seiichi Okabe et al. suggested that the administration of CUDC-907 might be a powerful strategy against myeloma cells, to enhance the cytotoxic effects of proteasome inhibitors. [Read the Full Post]

Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

373 | Mar 18 2021

Hao Zhou et al. demonstrated that curcumin exerted anti‑AML roles by inactivating AKT. [Read the Full Post]

Alpelisib: A Novel Therapy for Patients With PIK3CA- Mutated Metastatic Breast Cancer

236 | Mar 15 2021

Tori Wilhoit et al. thought that inhibition of PI3K was a promising new approach to overcome resistance to endocrine therapy in breast cancer. [Read the Full Post]

Wnt Activation After Inhibition Restores Trabecular Meshwork Cells Toward a Normal Phenotype

423 | Mar 15 2021

Kamesh Dhamodaran et al. found that, in normal hTM cells, activation of the Wnt pathway reversed the pathological phenotype caused by Wnt inhibition and might thus be a viable therapeutic for lowering IOP. [Read the Full Post]

Role of Alpelisib in the Treatment of PIK3CA-Mutated Breast Cancer: Patient Selection and Clinical Perspectives

215 | Mar 14 2021

Dwan-Ying Chang et al.updated and summarized the current state of the science, including the prognostic role of PIK3CA alterations in breast cancer; the evolution of PI3K inhibitors; the clinical utility of the first-in-class oral selective PI3Kα inhibitor, alpelisib. [Read the Full Post]

Sublethal irradiation promotes the metastatic potential of hepatocellular carcinoma cells

353 | Mar 08 2021

Yulin Cao et al. indicated that MMP-8 secreted by irradiated NPCs enhanced the migration and invasion of HCC by regulating AMPK/mTOR signaling, revealing a novel mechanism mediating sublethal irradiation-induced HCC metastasis at the level of the tumor microenvironment. [Read the Full Post]

Manipulating bovine granulosa cell energy metabolism limits inflammation

702 | Mar 03 2021

Anthony D Horlock et al. implied that energy stress compromised ovarian follicle immune defences. [Read the Full Post]

Inhibition of ATM induces hypersensitivity to proton irradiation by upregulating toxic end joining

439 | Feb 28 2021

Qin Zhou et al. found that inherent defects in HR or administration of an ATM inhibitor in HR proficient tumors selectively enhanced the relative biological effectiveness of proton Bragg peak irradiation. [Read the Full Post]

Combating TKI resistance in CML by inhibiting the PI3K/Akt/mTOR pathway in combination with TKIs: a review

251 | Feb 22 2021

Priyanka Singh et al. thought that the PI3K/Akt/mTOR signaling pathway in multiple cancers, might improve the therapeutic approaches towards TKI-resistant CML cells where the respective signaling pathway got upregulated. [Read the Full Post]

The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells

0 | Feb 21 2021

Kamira Maharaj et al. suggested that the improved safety profile of umbralisib was due to its role as a dual PI3Kδ/CK1ε inhibitor that preserved Treg number and function. [Read the Full Post]

Selective Elimination of Osteosarcoma Cell Lines with Short Telomeres by Ataxia Telangiectasia and Rad3-Related Inhibitors

393 | Feb 18 2021

Tomas Goncalves et al. provided a resource to identify links between the mode of telomere maintenance and drug sensitivity in osteosarcoma and indicated that telomere length predictd ATR inhibitor sensitivity in cancer. [Read the Full Post]

Immune checkpoint inhibition in syngeneic mouse cancer models by a silicasome nanocarrier delivering a GSK3 inhibitor

497 | Feb 17 2021

Sean D Allen et al. provided proof-of-principal demonstration of the feasibility of using encapsulated delivery of a GSK3 inhibitor to provide cancer immunotherapy, with the possibility to be used as a monotherapy or in combination with chemotherapy or other immunomodulatory agents. [Read the Full Post]

The apoptotic effect of GSK-3 inhibitors: BIO and CHIR 98014 on H1975 lung cancer cells through ROS generation and mitochondrial dysfunction

371 | Feb 07 2021

Theodore Lemuel Mathuram et al. found that the use of GSK-3 inhibitors showed promising apoptotic abilities in clinical cancer treatments, particularly for lung cancer cells. [Read the Full Post]

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

322 | Feb 04 2021

En Xu et al. suggested that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer. [Read the Full Post]

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition

1327 | Feb 02 2021

Sara Ibrahim et al. thought that rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3β pathway and inhibition of JNK signaling. [Read the Full Post]

Preclinical evaluation and Phase 1b study of prexasertib, a CHK1 inhibitor, and samotolisib (LY3023414), a dual PI3K/mTOR inhibitor

616 | Jan 27 2021

David S Hong et al found that Prexasertib+samotolisib showed antitumor activity in preclinical models and preliminary efficacy in heavily-pretreated patients. [Read the Full Post]

De novo protein synthesis is necessary for priming in preclinical models of migraine

887 | Jan 26 2021

Jacob Lackovic et al. suggested that targeting the regulation of protein synthesis might be a novel approach for new migraine treatment strategies. [Read the Full Post]

Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors

561 | Jan 07 2021

Chunlong Ma et al. suggested that these six compounds were nonspecific SARS-CoV-2 Mpro inhibitors and urged the scientific community to be stringent with hit validation. [Read the Full Post]

Inhibition of Phosphatidylinositol 3-Kinase γ by IPI-549 Attenuates Abdominal Aortic Aneurysm Formation in Mice

521 | Jan 04 2021

Rui Liu et al. found that inhibition of PI3Kγ limited AAA formation. Targeting PI3Kγ prevented inflammatory cell infiltration through inhibition of AKT phosphorylation in AAA. [Read the Full Post]

Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells

452 | Dec 22 2020

Xuejian Zhou et al. indicated that Artesunate induced autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells. [Read the Full Post]

AMPK mediates energetic stress-induced liver GDF15

488 | Dec 21 2020

Logan K Townsend et al. proved that AMPK played a role in mediating the induction of GDF15 under conditions of energetic stress in mouse liver in vivo. [Read the Full Post]

FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells

565 | Dec 20 2020

Yuan Zhong et al. provided a new perspective on the treatment of MM. [Read the Full Post]

Decreased activation of ataxia telangiectasia mutated (ATM) in monocytes from patients with systemic sclerosis

499 | Dec 18 2020

Komei Sakata et al. found that decreased ATM activation in monocytes was associated with SSc-interstitial lung disease and that impaired ATM activation in monocytes may contribute to the disease process of SSc via uncontrolled reactive oxygen species production. [Read the Full Post]

Establishment of multiplex allele-specific blocker PCR for enrichment and detection of 4 common EGFR mutations in non-small cell lung cancer

477 | Dec 18 2020

Hongyuan Chen et al. provided a solution for minor allele detection from ctDNA. [Read the Full Post]

Combination MEK and mTOR inhibitor therapy is active in models of glioblastoma

209 | Dec 03 2020

Karisa C Schreck et al. demonstrated that combined MEK/mTOR inhibition was synergistic in glioblastoma cell lines and might be more potent in NF1-deficient glioblastoma. [Read the Full Post]

Integrated pharmaco-proteogenomics defines two subgroups in isocitrate dehydrogenase wild-type glioblastoma with prognostic and therapeutic opportunities

354 | Dec 02 2020

Sejin Oh et al. guided GBM prognosis and precision treatment strategies. [Read the Full Post]

Rapalogues as hCES2A Inhibitors: In Vitro and In Silico Investigations

371 | Nov 17 2020

Cheng-Cheng Shi et al. demonstrated that several marketed rapalogues were potent and specific hCES2A inhibitors, and these agents could serve as leading compounds for the development of more efficacious hCES2A inhibitors to modulate the pharmacokinetic profiles and toxicity of hCES2A-substrate drugs (such as the anticancer agent irinotecan). [Read the Full Post]

CXCL14 inhibits the growth and promotes apoptosis of hepatocellular carcinoma cells via suppressing Akt/mTOR pathway

403 | Nov 17 2020

Jianqiang Bi et al. thought that CXCL14 inhibited growth but promoted apoptosis of HCC cells via suppressing Akt/mTOR pathway and CXCL14 might be a potential target for HCC treatment in clinical practice. [Read the Full Post]

A phase I trial of temsirolimus and erlotinib in patients with refractory solid tumors

734 | Nov 15 2020

Haeseong Park et al. found the he combination of temsirolimus and erlotinib at the RP2D was well tolerated, and the regimen resulted in prolonged disease stabilization in selected patients (NCT00770263). [Read the Full Post]

Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting

333 | Nov 05 2020

Alice Bradbury et al. thought that NIH-OVCAR3 cells highlighted the complexity of HGSOCs and that genomic or functional characterization alone might not be enough to predict/explain chemotherapy response. [Read the Full Post]

Small molecule 2,3-DCPE induces S phase arrest by activating the ATM/ATR-Chk1-Cdc25A signaling pathway in DLD-1 colon cancer cells

631 | Oct 29 2020

Bingjun Bai et al. suggested that 2,3-DCPE caused DNA damage in colon cancer cells and that 2,3-DCPE-induced S phase arrest was associated with the activation of the ATM/ATR-Chk1-Cdc25A pathway. [Read the Full Post]

EBV encoded miRNA BART8-3p promotes radioresistance in nasopharyngeal carcinoma by regulating ATM/ATR signaling pathway

302 | Oct 28 2020

Xiaohan Zhou et al. indicated that EBV-miR-BART8-3p promoted radioresistance in NPC by modulating the activity of ATM/ATR signaling pathway. [Read the Full Post]

mTOR Inhibition Ablates Cisplatin-Resistant Salivary Gland Cancer Stem Cells

377 | Oct 25 2020

T Nakano et al.suggested that a combination of an mTOR inhibitor and platinum-based chemotherapy might be beneficial to patients with salivary gland mucoepidermoid carcinoma. [Read the Full Post]

A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia

602 | Oct 22 2020

Fabian Lang et al.thought that combined inhibition of PI3K and mTOR inhibited a clinically meaningful driver pathway in a small subset of patients with ALL, with no benefit in patients with AML. [Read the Full Post]

HPV-induced Nurr1 promotes cancer aggressiveness, self-renewal, and radioresistance via ERK and AKT signaling in cervical cancer

569 | Oct 20 2020

Peter Kok-Ting Wan et al. provided that BEZ, but not GSK, could abolish Nurr1-enhanced radioresistance, suggesting its potential value for radiosensitizing CSLCs in the clinical setting. [Read the Full Post]

The PI3K/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis

271 | Oct 10 2020

Yangjiong Xiao et al. concluded that GSK458 might serve as an attractive candidate to treat ovarian cancer. [Read the Full Post]

Omipalisib Inhibits Esophageal Squamous Cell Carcinoma Growth Through Inactivation of Phosphoinositide 3-Kinase (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) and ERK Signaling

276 | Oct 05 2020

Dong-Shan Zhu et al. supported the rationale for using omipalisib as a therapeutic approach in ESCC patients. [Read the Full Post]

Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma

334 | Oct 05 2020

Monique Bernard et al. suggested a broader application for this combination therapy that could be promptly translated to in vivo studies. [Read the Full Post]

Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

512 | Oct 02 2020

Nicholas D LeBlond et al. suggested that intervention with the first-generation AMPK activator A-769662 was not able to stem the progression of atherosclerosis. [Read the Full Post]

Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells

297 | Sep 11 2020

Rebecca L Lloyd et al. provided a mechanistic understanding of combined PARP and ATR inhibition in ATM-deficient models, and supported the clinical development of AZD6738 in combination with olaparib. [Read the Full Post]

Inhibition of DNA-PKcs activity re-sensitizes uveal melanoma cells to radio- and chemotherapy

561 | Sep 03 2020

Bingjie Zhang et al. demonstrated increased DNA double strand break repair as a mechanism of resistance to ionizing radiation and Selumetinib, and identified DNA-PKcs as a promising target for radio-and chemotherapy in UM patients. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

0 | Sep 03 2020

Tong Zhou et al. suggested a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]

In Vitro and In Vivo Activity, Tolerability, and Mechanism of Action of BX795 as an Antiviral against Herpes Simplex Virus 2 Genital Infection

530 | Sep 02 2020

James Hopkins et al. revealed that the mechanism of action of BX795 antiviral activity stemed from the reduction of viral protein translation via inhibition of protein kinase B phosphorylation. [Read the Full Post]

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors

212 | Aug 28 2020

Daniel O Pinto et al. presented a novel approach allowing for the targeting of viral reservoirs, prevention of immune hyper-activation, and selectively killing latently infected HIV-1 cells. [Read the Full Post]

The mTORC1 inhibitor rapamycin and the mTORC1/2 inhibitor AZD2014 impair the consolidation and persistence of contextual fear memory

377 | Aug 23 2020

Phillip E MacCallum et al. indicated the need to further understand the role of mTORC1/2 kinase activity in the molecular mechanisms underlying memory processing and also demonstrated that the effects of mTORC1 inhibition at different timepoints well after learning on memory consolidation and persistence. [Read the Full Post]

The impact of autophagy on arbovirus infection of mosquito cells

297 | Aug 20 2020

Doug E Brackney et al. suggested that commonly used chemical modulators of autophagy alter mosquito cells in such a way as to promote viral replication. [Read the Full Post]

A phase 2 trial of buparlisib in patients with platinum-resistant metastatic urothelial carcinoma

383 | Aug 17 2020

Victor McPherson et al. proposed that given the modest clinical activity and substantial toxicity of buparlisib, future trials of PI3K inhibitors in patients with UC should focus on isoform-selective PI3K inhibitors in genomically selected patients. [Read the Full Post]

The role of CUDC-907, a dual phosphoinositide-3 kinase and histone deacetylase inhibitor, in inhibiting proliferation of adult T-cell leukemia

307 | Aug 17 2020

Chie Ishikawa et al. showed that CUDC-907 might be a potential therapeutic agent for ATL. [Read the Full Post]

Macrophages confer resistance to PI3K inhibitor GDC-0941 in breast cancer through the activation of NF-κB signaling

437 | Aug 13 2020

Muhammad Waqas Usman et al. suggested macrophages in microenvironment may contribute to the resistance of breast cancer cells to PI3K inhibition and reveal a new combination paradigm to improve the efficacy of PI3K-targeted therapy. [Read the Full Post]

A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration

435 | Aug 12 2020

Alexia Hervieu et al. revealed a GTPase-independent role for Rac1 in mediating a PI3K-independent MET-to-mTOR pathway and suggested alternative or combined strategies that might overcome resistance to RTK inhibitors in patients with cancer. [Read the Full Post]

Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway

679 | Aug 10 2020

Jingyu Deng et al. showed that Irisin played a significant role in anti-apoptosis, anti-inflammation, anti-oxidative stress in HG-induced CMs via AMPK/mTOR signaling pathway. [Read the Full Post]

Severe COVID-19 in a renal transplant recipient: A focus on pharmacokinetics

662 | Aug 08 2020

Soufian Meziyerh et al. aimed to achieve increased awareness and improved management of drug-drug interactions associated with the various treatment options for COVID-19 in renal transplant patients. [Read the Full Post]

Pentraxin-3 Mediates Prosurvival Actions of Interferon Tau in Bovine Luteinized Granulosa Cells

681 | Aug 06 2020

Raghavendra Basavaraja et al. suggested a novel role for PTX3 during early pregnancy, as mediator of IFNT prosurvival actions supporting CL maintenance during this reproductive stage. [Read the Full Post]

Pharmacokinetics and bioavailability of ipatasertib in dog plasma using LC/MS/MS

437 | Jul 27 2020

Ying Liu et al. showed that the bioavailability of ipatasertib was determined to be 19.3%. [Read the Full Post]

Combined inhibition of ACK1 and AKT shows potential toward targeted therapy against KRAS-mutant non-small-cell lung cancer

445 | Jul 27 2020

Xiangjing Yu et al. demonstrated the promising therapeutic potential of combined ACK1/AKT inhibition as a strategy against KRAS-mutant NSCLC. [Read the Full Post]

Copanlisib for the Treatment of Adults With Relapsed Follicular Lymphoma

276 | Jul 09 2020

Massimo Magagnoli et al. found that teatment with copanlisib results in clinically relevant and durable responsed in heavily pretreated patients with relapsed or refractory FL. [Read the Full Post]

Inhibition of PI3K by Copanlisib Exerts Potent Antitumor Effects on Merkel Cell Carcinoma Cell Lines and Mouse Xenografts

264 | Jul 09 2020

Bin Fang et al. provided compelling preclinical evidence for application of copanlisib in advanced MCC with aberrant PI3K activation for which immunotherapy was insufficient, or patients who were unsuitable for immunotherapy. [Read the Full Post]

The Dual PI3Kδ/CK1ε Inhibitor Umbralisib Exhibits Unique Immunomodulatory Effects on CLL T Cells

569 | Jul 08 2020

Kamira Maharaj et al. suggested that the improved safety profile of umbralisib was due to its role as a dual PI3Kδ/CK1ε inhibitor that preserved Treg number and function. [Read the Full Post]

Berzosertib Plus Gemcitabine Versus Gemcitabine Alone in Platinum-Resistant High-Grade Serous Ovarian Cancer: A Multicentre, Open-Label, Randomised, Phase 2 Trial

412 | Jul 06 2020

Panagiotis A Konstantinopoulos et al. showed a benefit of adding berzosertib to gemcitabine in platinum-resistant high-grade serous ovarian cancer. [Read the Full Post]

The Gαh/phospholipase C-δ1 Interaction Promotes Autophagosome Degradation by Activating the Akt/mTORC1 Pathway in Metastatic Triple-Negative Breast Cancer

341 | Jul 05 2020

Hui-Yu Lin et al. demonstrated that the induction of autophagy activity or the inhibition of Akt-mTORC1 axis provided a useful strategy to combat the Gαh/PLC-δ1-driven LM of TNBC. [Read the Full Post]

Effect of Morphology on the Photoelectrochemical Performance of Nanostructured Cu2O Photocathodes

447 | Jul 05 2020

Lian C T Shoute found that although different deposition methods showed a similar average photocurrent density 2.8±0.3 mA/cm2 at 0 V vs RHE, large variations in the photocurrent density were observed for samples prepared under nominally identical deposition methods. [Read the Full Post]

Differential Therapeutic Effects of PARP and ATR Inhibition Combined With Radiotherapy in the Treatment of Subcutaneous Versus Orthotopic Lung Tumour Models

345 | Jul 02 2020

Vanessa Tran Chau et al. highlighted the importance of using more pathologically relevant models, such as syngeneic orthotopic models, to determine the most appropriate therapeutic approaches for translation to the clinic. [Read the Full Post]

Volumetric Absorptive Microsampling (VAMS) for Assaying Immunosuppressants From Venous Whole Blood by LC-MS/MS Using a Novel Atmospheric Pressure Ionization Probe (UniSpray™)

1747 | Jun 28 2020

Lucía Paniagua-González et al. showed that venous blood VAMS concentrations were correlated to those found in the original liquid venous blood, proving that the VAMS material itself will not bias blood drug concentrations. [Read the Full Post]

Effects of the PI3K/Akt Signaling Pathway on the Apoptosis of Early Host Cells Infected With Eimeria Tenella

1239 | Jun 21 2020

Xuesong Zhang et al. investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella,the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. [Read the Full Post]

Calcium Signaling Mediated by Aminergic GPCRs Is Impaired by the PI3K Inhibitor LY294002 and Its Analog LY303511 in a PI3K-independent Manner

333 | Jun 13 2020

Polina D Kotova et al. found that LY303511 and LY294002 should be used cautiously in studies of PI3K as a factor of GPCR signaling. [Read the Full Post]

Generation of Liver Bipotential Organoids With a Small-Molecule Cocktail

811 | Jun 05 2020

Xin Wang et al. demonstrated that Wnt/β-catenin, NMII-Rac, and PKA-ERK are core signaling pathways essential and sufficient for mouse liver progenitor expansion. [Read the Full Post]

Phase I Trial of Alpelisib in Combination With Concurrent Cisplatin-Based Chemoradiotherapy in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

263 | Jun 03 2020

D Day et al. found that Alpelisib at 200 mg has a manageable safety profile in combination with cisplatin-based CRT in LA-SCCHN. [Read the Full Post]

The Novel Dual BET/HDAC Inhibitor TW09 Mediates Cell Death by Mitochondrial Apoptosis in Rhabdomyosarcoma Cells

295 | Jun 03 2020

Stephanie Laszig et al. found that TW09 showed potent antitumor activity in RMS cells in vitro by inducing mitochondrial apoptosis and might represent a promising new therapeutic option for the treatment of RMS. [Read the Full Post]

Cell Cycle Arrest and Apoptosis Are Not Dependent on p53 Prior to p53-dependent Embryonic Stem Cell Differentiation

1245 | Jun 02 2020

Sushil K Jaiswal et al. found that the multiple roles of p53 in cell cycle regulation and apoptosis were first acquired during pluripotent stem cell differentiation. [Read the Full Post]

Phase II Trial of AKT Inhibitor MK-2206 in Patients With Advanced Breast Cancer Who Have Tumors With PIK3CA or AKT Mutations, and/or PTEN loss/PTEN Mutation

582 | May 31 2020

Yan Xing et al. found that MK-2206 monotherapy had limited clinical activity in advanced breast cancer patients selected for PIK3CA/AKT1 or PTEN mutations or PTEN loss. This may, in part, be due to inadequate target inhibition at tolerable doses in heavily pre-treated patients with pathway activation, as well as tumor heterogeneity and evolution in markers such as PTEN conferring challenges in patient selection. [Read the Full Post]

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island

0 | May 24 2020

Sebastian I Arriola Apelo et al. discussed recent advances in understanding the molecular and physiological effects of rapamycin treatment, and they discussed how the use of alternative rapamycin treatment regimens or rapamycin analogs had the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. [Read the Full Post]

Discovery of suppressors of CRMP2 phosphorylation reveals compounds that mimic the behavioral effects of lithium on amphetamine-induced hyperlocomotion

497 | May 18 2020

Zhao WN et al. not only provided insights into the neural substrates regulated by lithium, but also provided novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders. [Read the Full Post]

Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway

380 | May 11 2020

Wei H et al. suggested that KLK10 silencing may attenuate the progression of CRC by inhibiting cell growth and glycolysis via the PI3K/AKT/mTOR signaling, supporting a potential and promising target for CRC therapy. [Read the Full Post]

Attenuation of canonical NF-κB signaling maintains function and stability of human Treg

900 | May 11 2020

Ziegler LS et al. provided first insights into the role of NF-κB signaling in human Treg. [Read the Full Post]

FAM83A Promotes Lung Cancer Progression by Regulating the Wnt and Hippo Signaling Pathways and Indicates Poor Prognosis

487 | May 07 2020

Zheng YW et al. found that FAM83A promotes the proliferation and invasion of lung cancer cells by regulating the Wnt and Hippo signaling pathways and EMT process. [Read the Full Post]

FOXK1 Promotes Proliferation and Metastasis of Gallbladder Cancer by Activating AKT/mTOR Signaling Pathway

416 | May 07 2020

Wencong M et al. suggested that FOXK1 promotes GBC cells progression and represent a novel prognostic biomarker and potential therapeutic target in GBC. [Read the Full Post]

GSK-3 Inhibitors: A Double-Edged Sword? - An Update on Tideglusib

525 | May 05 2020

Mathuram TL et al. concluded the emergence of GSK-3 inhibitors as a 'double-edged sword' in the treatment against human diseases cautioning researchers about the potential ramifications of off-target pharmacological effects. [Read the Full Post]

Inhibiting PI3 kinase-γ in both myeloid and plasma cells remodels the suppressive tumor microenvironment in desmoplastic tumors

651 | May 03 2020

Zhang X et al. concluded that IPI-549 NP delivery could be a promising method for treating pancreatic cancer and other immune-suppressive tumors. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 | Mar 30 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

Bcl-2high mantle cell lymphoma cells are sensitized to acadesine with ABT-199

389 | Mar 23 2020

Montraveta A et al. supported the notions that antiapoptotic proteins of the Bcl-2 family regulate MCL cell sensitivity to acadesine and that the combination of this agent with Bcl-2 inhibitors might be an interesting therapeutic option to treat MCL patients. [Read the Full Post]

Biguanides Induce Acute de novo Lipogenesis in Human Primary Sebocytes

382 | Mar 22 2020

Nicoll J et al. found that biguanides, isotretinoin and azithromycin induced an acute dose and time-dependent increase in [14C]-acetate labeling of neutral lipids, while AICAR, an AMPK activator, inhibited this DNL response. Biguanides did not activate AMPK in sebocytes, however, they significantly reduced oxygen consumption rate and increased lactate production. Treatment with biguanides, but not isotretinoin, significantly upregulated ACSS2 gene expression in primary sebocytes and showed synergism with lipogenic activators to induce DNL genes. [Read the Full Post]

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

460 | Mar 16 2020

Tian X et al.demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment. [Read the Full Post]

Structure of the intact ATM/Tel1 kinase

503 | Mar 16 2020

Wang X et al. provided a structural framework for understanding the mechanisms of ATM/Tel1 regulation as well as the development of new therapeutic agents. [Read the Full Post]

ATM induces MacroD2 nuclear export upon DNA damage

549 | Mar 13 2020

Golia B et al. identified a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

0 | Feb 16 2020

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo

421 | Feb 12 2020

Ribas R et al. supported the combination of AZD5363 with fulvestrant as a potential therapy for breast cancer that is sensitive or resistant to E-deprivation or tamoxifen and that activated AKT is a determinant of response, supporting the need for clinical evaluation. [Read the Full Post]

G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma

278 | Feb 06 2020

Yu Z et al. indicated that the combined G250-TNBs and UTND treatment can deliver anti-tumor drugs to local areas of RCC, increase the local effective drug concentration, and enhance anti-tumor efficacy, thus providing a potential novel method for targeted therapy of RCC. [Read the Full Post]

Rapamycin ester analog CCI-779/Temsirolimus alleviates tau pathology and improves motor deficit in mutant tau transgenic mice

325 | Feb 06 2020

Frederick C et al. indicated that stimulation of mTOR dependent autophagy by CCI-779 compound is efficient to counteract the accumulation of abnormal tau when administered early or late in a tauopathy model and to improve a motor deficit when started before onset of motor signs. [Read the Full Post]

Analyses of FGFR3 and PIK3CA mutations in neuroblastomas and the effects of the corresponding inhibitors on neuroblastoma cell lines

318 | Jan 31 2020

Kostopoulou ON et al. demonstrated that FGFR3 and PIK3CA mutations are uncommon in patients with NB. [Read the Full Post]

Melatonin alleviates hypoxia-induced cardiac apoptosis through PI3K/Akt pathway

442 | Jan 19 2020

Luo GP et al. demonstrated that melatonin confers cardioprotection by inhibiting apoptosis through the activation of PI3K/Akt signaling pathway in hypoxic cardiomyocytes. [Read the Full Post]

Preclinical evaluation of drug combinations identifies co-inhibition of Bcl-2/XL/W and MDM2 as a potential therapy in uveal melanoma

0 | Jan 16 2020

Clapes V et al. showed that inhibition of Bcl-2/XL/W sensitised the UM cell lines to other treatments encouraging investigation of the underlying mechanisms. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

0 | Jan 12 2020

Hendriks CMM et al. suggested that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. [Read the Full Post]

Adverse Drug Reactions Involving Protein Kinase Inhibitors: A French Pharmacovigilance Database Study Comparing Safety in Younger and Older Patients (≥ 75 years) with Cancer

302 | Jan 11 2020

Clapes V et al. showed that PKI-related ADRs in older patients were similar to those in younger adults, except for vascular ADRs, which were significantly more frequent in the older population. [Read the Full Post]

PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells

613 | Jan 06 2020

Wang Y et al. revealed that LY294002 displays the opposite effect on PI3K-dependent AKT phosphorylation, which maintains cell survival from the cytotoxicity introduced by LY294002 itself in GEM-resistant pancreatic cancer cells. We suggest that targeting the PI3K/AKT signaling pathway with inhibitors may be counterproductive for patients with PC who have acquired GEM-resistance. [Read the Full Post]

Predictability, efficacy and safety of radiosensitization of glioblastoma-initiating cells by the ATM inhibitor KU-60019

453 | Jan 05 2020

Vecchio D et al. suggested that GIC-driven tumors with low expression of TP53 and high expression of PI3K might be effectively and safely radiosensitized by KU-60019. [Read the Full Post]

Biomarkers of response and resistance to PI3K inhibitors in estrogen receptor-positive breast cancer patients and combination therapies involving PI3K inhibitors

281 | Jan 04 2020

Brandão M at al. described the rational for new combination therapies involving PI3Ki and anti-HER2 agents, chemotherapy, CDK4/6 inhibitors, mTOR inhibitors or new endocrine treatments and discuss the ongoing trials in this field. [Read the Full Post]

AZD8055 Exerts Antitumor Effects on Colon Cancer Cells by Inhibiting mTOR and Cell-cycle Progression

398 | Dec 26 2019

Chen Y et al. indicated that AZD8055 induces cytotoxicity, apoptosis, and cell-cycle arrest of colon cancer cells, and exerts an antitumor effect in mice. It also inhibits the mTOR signaling pathway and mTOR-dependent cell-cycle progression. [Read the Full Post]

NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma

567 | Dec 24 2019

Huang JC et al. suggested NVP-BEZ235 could synergize cisplatin sensitivity in OS, combination of NVP-BEZ235 with cisplatin could represent a novel therapeutic strategy for treatment of OS. [Read the Full Post]

The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia

484 | Dec 24 2019

Deng L et al. indicated that the PI3K/mTOR dual inhibitor BEZ235 effectively chemosensitizes AML cells via increasing miR-1-3p and subsequently down-regulating BAG4, EDN1 and ABCB1. [Read the Full Post]

Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models

533 | Dec 23 2019

Netland IA et al. suggested that despite the anti-neoplastic efficacy of dactolisib in glioma treatment in vitro, its utility in vivo is questionable due to toxicity. [Read the Full Post]

First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies

306 | Dec 15 2019

Munster P et al. indicated although the MTD of GSK458 was 2.5 mg once daily, twice-daily dosing may increase duration of target inhibition. Fasting insulin and glucose levels served as pharmacodynamic markers of drug exposure. Select patients achieved durable responses; however,PIK3CAmutations were neither necessary nor predictive of response. Combination treatment strategies and novel biomarkers may be needed to optimally target PI3K. [Read the Full Post]

PI3K inhibition reduces murine and human liver fibrogenesis in precision-cut liver slices

311 | Dec 12 2019

Gore E et al. showed that omipalisib has antifibrotic properties in ex vivo mouse and human liver PCTS, but higher concentrations showed toxicity in jejunum PCTS. While the PI3K/mTOR pathway appears to be a promising target for the treatment of liver fibrosis, PCTS revealed likely side effects in the intestine at higher doses. [Read the Full Post]

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

410 | Dec 12 2019

Mercer PF et al. indicated the data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-of-mechanism trial of this agent is currently underway. [Read the Full Post]

Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

657 | Dec 09 2019

Rameshrad M et al. demonstrated that activation of AMPK, by A-769662 agent, could inhibit Tlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue. [Read the Full Post]

Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system

553 | Nov 27 2019

Xu J et al. demonstrated that stable iPS cells could be generated in LCDM medium, which could give rise to both embryonic and extraembryonic cells in vivo. However, the efficiency and level of chimeric contribution of pig LCDM-iPS cells were found low. [Read the Full Post]

Isolation of induced pluripotent stem cell-derived endothelial progenitor cells from sac-like structures

594 | Nov 27 2019

Aoki H et al. improved regenerative medicine and facilitate basic studies on the endothelial lineage. [Read the Full Post]

Y-27632 preserves epidermal integrity in a human skin organ-culture (hSOC) system by regulating AKT and ERK signaling pathways

468 | Nov 23 2019

Zhang X et al. found that Y-227632 can maintain skin epidermal integrity through regulation of AKT and ERK activity in the hSOC. [Read the Full Post]

The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma

423 | Nov 16 2019

Hanna DL et al. reported a case in which a renal transplant recipient with metastatic melanoma had an excellent response to treatment with second line programmed cell death protein 1 (PD-1) inhibitor therapy, pembrolizumab. [Read the Full Post]

NU7441 Enhances the Radiosensitivity of Liver Cancer Cells

598 | Nov 15 2019

Yang C et al. showed that NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

0 | Nov 15 2019

Zhou T et al. indicated this chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]

BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells

758 | Nov 14 2019

Su AR et al. identified the anti-HSV activity of BX-795 and its targeting of the JNK/p38 MAP kinase pathways in host cells. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

0 | Nov 08 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128 might be further investigated as a novel anti-OS agent. [Read the Full Post]

Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice

299 | Nov 08 2019

Zhang S et al. suggested that mTOR kinase inhibitors may be beneficial for the treatment of ICC, even in tumors that are resistant to standard of care chemotherapeutics, such as gemcitabine/oxaliplatin-based regimens, especially in the subset of tumors exhibiting activated AKT/mTOR cascade. Lay summary: We established a novel mouse model of intrahepatic cholangiocarcinoma (ICC). Using this new preclinical model, we evaluated the therapeutic potential of mTOR inhibitor MLN0128 vs. gemcitabine/oxaliplatin (the standard chemotherapy for ICC treatment). Our study shows the anti-neoplastic potential of MLN0128, suggesting that it may be superior to gemcitabine/oxaliplatin-based chemotherapy for the treatment of ICC, especially in the tumors exhibiting activated AKT/mTOR cascade. [Read the Full Post]

CHIR-99021 regulates mitochondrial remodelling via β-catenin signalling and miRNA expression during endodermal differentiation

1074 | Nov 05 2019

Ma Y et al. demonstrated that CHIR-99021 plays a role in mitochondrial structure and function remodelling via activation of the β-catenin signalling pathway and inhibits the expression of miRNAs during definitive endodermal differentiation. [Read the Full Post]

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules

0 | Nov 01 2019

Guichard SM et al. indicated the ability to dose AZD2014 intermittently, together with its ability to block signaling from both mTORC1 and mTORC2 complexes, makes this compound an ideal candidate for combining with endocrine therapies in the clinic. AZD2014 is currently in phase II clinical trials. [Read the Full Post]

Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model

445 | Oct 30 2019

Cheng NT et al. demonstrated that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA.Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. [Read the Full Post]

NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction

0 | Oct 28 2019

Yang S et al. demonstrated a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications. [Read the Full Post]

Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial

409 | Oct 25 2019

Baselga J et al. showed that PI3K inhibition combined with endocrine therapy is effective in postmenopausal women with endocrine-resistant, hormone receptor-positive and HER2-negative advanced breast cancer. Use of more selective PI3K inhibitors, such as α-specific PI3K inhibitor, is warranted to further improve safety and benefit in this setting. No further studies are being pursued because of the toxicity associated with this combination. [Read the Full Post]

BKM120 induces apoptosis and inhibits tumor growth in medulloblastoma

396 | Oct 25 2019

Zhao P et a. indicated that these findingshelp to establish a basis for clinical trials of BKM120, which could be a novel therapy for the treatment of medulloblastoma patients. [Read the Full Post]

The PI3K inhibitor GDC-0941 enhances radiosensitization and reduces chemoresistance to temozolomide in GBM cell lines

415 | Oct 22 2019

Shi F et al. suggested that the combination of TMZ, IR, and GDC-0941 is a promising choice for future treatments of GBM. [Read the Full Post]

The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer

340 | Oct 21 2019

Zeng SX et al. provided new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. [Read the Full Post]

Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels

400 | Oct 19 2019

Li N et al. indicated that dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance. Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer. [Read the Full Post]

Clinical relevance of a CD4+ T cell immune function assay in the diagnosis of infection in pediatric living-donor liver transplantation

0 | Oct 14 2019

Liu W et al. suggested that low CD4+ T lymphocyte ATP levels may be an independent risk factor for infection following pediatric LDLT, and that the Immuknow assay may be used as a tool to evaluate T lymphocyte function in such patients to predict the risk of infection. [Read the Full Post]

Clinical relevance of a CD4+ T cell immune function assay in the diagnosis of infection in pediatric living-donor liver transplantation

0 | Oct 14 2019

Liu W et al. suggested that low CD4+ T lymphocyte ATP levels may be an independent risk factor for infection following pediatric LDLT, and that the Immuknow assay may be used as a tool to evaluate T lymphocyte function in such patients to predict the risk of infection. [Read the Full Post]

NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction

356 | Oct 12 2019

Yang S et al. demonstrated a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications. [Read the Full Post]

Targeting the PI3K/Akt/mTOR-pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases

504 | Oct 08 2019

Ippen FM et al. suggested that the Akt-inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway. These data provide a rationale to further evaluate the efficacy of GDC-0068 in patients with brain metastases. [Read the Full Post]

AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells

620 | Oct 04 2019

Min A et al. suggested synthetic lethality between ATR inhibition and ATM deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM deficiency are warranted to develop novel treatment strategies for gastric cancer. [Read the Full Post]

Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

669 | Oct 03 2019

Kim SB et al. supported AKT-targeted therapy for triple-negative breast cancer. Ipatasertib warrants further investigation for the treatment of triple-negative breast cancer. [Read the Full Post]

Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma

410 | Sep 21 2019

Dreyling M et al. demonstrated promising efficacy and manageable toxicity in heavily pretreated patients with various subtypes of indolent and aggressive malignant lymphoma. Subtype-specific studies of copanlisib in patients with follicular, peripheral T-cell, and mantle cell lymphomas are ongoing. [Read the Full Post]

Copanlisib: An Intravenous Phosphatidylinositol 3-Kinase (PI3K) Inhibitor for the Treatment of Relapsed Follicular Lymphoma

0 | Sep 19 2019

Eltantawy A et al. provided an alternative option for patients with relapsed FL. It is safe and effective and has an acceptable toxicity profile. [Read the Full Post]

Copanlisib: First Global Approval

0 | Sep 18 2019

Markham A summarizes the milestones in the development of copanlisib leading to this first approval for relapsed follicular lymphoma. [Read the Full Post]

The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia

276 | Sep 16 2019

Hoellenriegel J et al. provided an explanation for the clinical activity of CAL-101, and a roadmap for future therapeutic development. [Read the Full Post]

GS-1101: a delta-specific PI3K inhibitor in chronic lymphocytic leukemia

325 | Sep 16 2019

Macias-Perez IM et al. indicated this article will review new insights into the pathophysiology of CLL, the preclinical rationale of a PI3Kδ inhibitor in CLL, and the clinical evidence supporting this first-in-class therapeutic target for CLL patients. [Read the Full Post]

Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation

475 | Sep 12 2019

Fokas E et al. support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC. [Read the Full Post]

Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier dysfunction in acute lung injury

476 | Sep 11 2019

Slavin SA et al. indicated these data imply a role of autophagy in lung vascular injury and reveal the protective and therapeutic utility of 3-MA against ALI. [Read the Full Post]

Synthesis and screening of 3-MA derivatives for autophagy inhibitors

488 | Sep 11 2019

Wu Y et al. demonstrated that chemical modification of an existing autophagy inhibitor is an effective method to generate improved autophagy inhibitors. [Read the Full Post]

BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma

924 | Sep 07 2019

Gobin B et al. indicated the present work shows that BYL719 is a promising drug in either a single or multidrug approach to curing bone sarcoma. [Read the Full Post]

Effects of EF-24, RAD001, and paclitaxel on the expression profiles of apoptotic and anti-apoptotic genes

0 | Aug 26 2019

Alp E et al. showed that response of these cells to paclitaxel, EF-24, and RAD001 was found different at the transcriptional level of apoptotic and antiapoptotic genes. Therefore, understanding transcriptional changes after these drug exposure may give us a change to figure out more realistic results of the apoptotic pathway inhibition. [Read the Full Post]

Doxorubicin as a fluorescent reporter identifies novel MRP1 (ABCC1) inhibitors missed by calcein-based high content screening of anticancer agents

471 | Aug 13 2019

Sampson A et al. indicated mifepristone and doramapimod as pan inhibitors of these three drug transporters while celecoxib exhibited selective MRP1 inhibition. Together, our findings signify the importance of MRP1 in drug discovery and demonstrate the effectiveness and value of doxorubicin-based high content screening approach. Anti-cancer agents that exhibit MRP1 inhibition may be used to reverse multidrug resistance or to improve the efficacy and reduce the toxicity of various cancer chemotherapies. On the other hand, anti-cancer drugs that did not interact with MRP1 carry a low risk for developing MRP1-mediated resistance. [Read the Full Post]

Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity

596 | Aug 03 2019

Katsuda T et al. reported that a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs). CLiPs can differentiate into both MHs and biliary epithelial cells that can form functional ductal structures. CLiPs in long-term culture did not lose their proliferative capacity or their hepatic differentiation ability, and rat CLiPs were shown to extensively repopulate chronically injured liver tissue. Thus, our study advances the goals of liver regenerative medicine. [Read the Full Post]

A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer

0 | Jul 31 2019

Mayer IA et al. showed that alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%-56%), including five objective responses. Of eight patients remaining on treatment ≥12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER+/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro CONCLUSIONS: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER+ breast cancer are ongoing. [Read the Full Post]

A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or III PIK3CA-Mutant ER-Positive and HER2-Negative Breast Cancer

550 | Jul 24 2019

Ma CX et al. indicated that MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA-mutant ER+ breast cancer and should not be studied further in the target patient population. [Read the Full Post]

Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island

649 | Jul 21 2019

Arriola Apelo SI et al. discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging. [Read the Full Post]

Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors

0 | Jul 18 2019

Naujok O et al. indicated that out of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity. [Read the Full Post]

Signaling pathways and inhibitors of cells from patients with kaposiform lymphangiomatosis

411 | Jul 13 2019

Boscolo E et al. demonstrated that cells from KLA patient lesions are highly proliferative and the PI3K-AKT-mTOR and MAPK pathways are promising therapeutic targets. [Read the Full Post]

Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery

714 | Jun 27 2019

Colclough N et al. demonstrated how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders. [Read the Full Post]

The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development

695 | Jun 04 2019

Xing T et al. indicated that PDPK-1 and other intrinsic kinases downstream of IGF-1 are key regulators of rod photoreceptor formation. [Read the Full Post]

CCI-779 (Temsirolimus) exhibits increased anti-tumor activity in low EGFR expressing HNSCC cell lines and is effective in cells with acquired resistance to cisplatin or cetuximab

341 | May 27 2019

Niehr F et al. indicated that activity of CCI-779 in HNSCC cells harboring TP53 mutations and displaying a phenotype of cisplatin resistance suggests its clinical potential even in patients with dismal outcome after current standard treatment. Cetuximab/mTORi combinations might be useful for treatment of tumors with high expression of EGFR/p-EGFR and/or acquired cetuximab resistance. This combinatorial treatment modality needs further evaluation in future translational and clinical studies. [Read the Full Post]

AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner

808 | May 23 2019

Vlachaki Walker JM et al. indicated that AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway. [Read the Full Post]

Low-intensity pulsed ultrasound promotes the proliferation of human bone mesenchymal stem cells by activating PI3K/AKt signaling pathways

589 | May 18 2019

Xie S et al. suggested that LIPUS exposure may be involved in the proliferation of hBMSCs via activation of the PI3K/AKt signaling pathway and high expression of cyclin D1, and the intensity of 50 or 60 mW/cm2 and exposure time of 5 minutes were determined to be the optimal parameters for LIPUS exposure. [Read the Full Post]

Update Breast Cancer 2019 Part 2 - Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice

411 | May 10 2019

This review summarises the latest studies and publications and evaluates them in regard to the relevance for clinical practice. [Read the Full Post]

Puromycin based inhibitors of aminopeptidases for the potential treatment of hematologic malignancies

441 | May 08 2019

Singh R et al. indicated that effective inhibitors of Puromycin-Sensitive Aminopeptidase (PSA) are di sclosed here. These potential therapeutic agents display superior in vitro antitumor potency against two leukemic cell lines, as compared to known inhibitors of aminopeptidases. [Read the Full Post]

Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models

441 | Apr 23 2019

Wang D et al. developed and validated the first TAC PPK model for patients with PRNS. The study also provided a summary of previous literature concerning other TAC PPK models in different pediatric diseases. [Read the Full Post]

The dual PI3K/mTOR inhibitor GSK2126458 is effective for treating solid renal tumours in Tsc2+/- mice through suppression of cell proliferation and induction of apoptosis

0 | Apr 19 2019

Narov K et al. found that both GSK2126458 and rapamycin caused significant reduction in number and size of solid renal tumours. GSK2126458 also significantly reduced the number and size of all lesions (cystic, papillary and solid) although to a lesser extent compared to rapamycin. GSK2126458 inhibited both PI3K and mTOR while rapamycin exerted stronger inhibitory effect on mTORC1 in renal tumours. Furthermore, GSK2126458 and rapamycin suppressed proliferation of tumour cells. Importantly, GSK2126458 increased apoptosis of solid tumours but rapamycin did not. Further investigations are therefore needed to test whether rapamycin in combination with GSK2126458 could promote apoptosis and thus improve therapy of TSC-associated renal tumours. [Read the Full Post]

The HSP90 inhibitor, NVP-AUY922, attenuates intrinsic PI3K inhibitor resistance in KRAS-mutant non-small cell lung cancer

471 | Apr 19 2019

Park KS et al. indicated that dual inhibition of the HSP90 and PI3K signaling pathways with sub-therapeutic doses of these combined anticancer drugs may represent a potent treatment strategy for KRAS-mutant NSCLC with intrinsic resistance to PI3K inhibition. [Read the Full Post]

Copanlisib: An Intravenous Phosphatidylinositol 3-Kinase (PI3K) Inhibitor for the Treatment of Relapsed Follicular Lymphoma

554 | Apr 18 2019

Eltantawy A et al. indicated Copanlisib provides an alternative option for patients with relapsed FL. It is safe and effective and has an acceptable toxicity profile. [Read the Full Post]

Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models

700 | Apr 17 2019

Kuk MU et al. indicated that the mitochondrial functional recovery by ATM inhibition might represent a promising strategy to ameliorate the accelerated aging phenotypes and to treat age-related disease. [Read the Full Post]

Sublingual tacrolimus as an alternative to oral administration for solid organ transplant recipients

425 | Apr 16 2019

Pennington CA et al. indicated that in addition to enteral tube and i.v. tacrolimus dosing, sublingual administration may be considered for short-term use in patients who are unable to receive medications orally. Based on the available data, it is reasonable to initiate sublingual tacrolimus at 50% of the current or anticipated oral dose in the absence of interacting medications. Dosing must be individualized, taking into consideration concomitant interacting medications, and adjusted to target levels based on therapeutic drug monitoring. [Read the Full Post]

Chemoproteomic Selectivity Profiling of PIKK and PI3K Kinase Inhibitors

432 | Apr 12 2019

Reinecke M et al. showed that NVP-BEZ235 is not a PI3K inhibitor. Surprisingly, the designated ATM inhibitor CP466722 was found to bind strongly to ALK2, identifying a new chemotype for drug discovery to treat fibrodysplasia ossificans progressiva. [Read the Full Post]

Copanlisib: First Global ApprovalMarkham A

440 | Apr 11 2019

Markham A had summarize the milestones in the development of copanlisib leading to this first approval for relapsed follicular lymphoma. [Read the Full Post]

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

460 | Apr 06 2019

Rubie C et al. concluded that mTOR signaling through TORC1 may be affected in the regulation of T2DM. [Read the Full Post]

Oncogenic role of ABHD5 in endometrial cancer

715 | Apr 04 2019

Zhou Q suggested that ABHD5 may play an oncogenic role in endometrial cancer via the AKT pathway. [Read the Full Post]

White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

672 | Apr 03 2019

Yang Y et al. demonstrated that GSK-3-mediated GR/RORα signaling pathway is involved in white LED light-induced autophagy in hippocampal neuron cells. [Read the Full Post]

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules

0 | Apr 01 2019

Guichard SM et al. indicated the ability to dose AZD2014 intermittently, together with its ability to block signaling from both mTORC1 and mTORC2 complexes, makes this compound an ideal candidate for combining with endocrine therapies in the clinic. AZD2014 is currently in phase II clinical trials. [Read the Full Post]

DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin

892 | Mar 26 2019

Ciszewski WM et al. indicated that DNA-PK might be an effective target for chemo- and radio-potentiation in breast cancer and suggest that further development of DNA-PK inhibitors for clinical use is warranted. [Read the Full Post]

Tyrosyl-DNA phosphodiesterase and the repair of 3'-phosphoglycolate-terminated DNA double-strand breaks

996 | Mar 26 2019

Zhou T et al. indicated This chromosomal hypersensitivity, as well as a small but reproducible enhancement of calicheamicin cytotoxicity following siRNA-mediated TDP1 knockdown, suggests a role for TDP1 in repair of 3'-PG double-strand breaks in vivo. [Read the Full Post]

Monitoring the Activation of the DNA Damage Response Pathway in a 3D Spheroid Model

646 | Mar 15 2019

Mondesert O et al. demonstrated that DDR activation and its pharmacological manipulation with inhibitory and activatory compounds can be efficiently monitored in live 3D spheroid model. [Read the Full Post]

Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models

756 | Mar 11 2019

Toren P et al. provided preclinical data to support evaluation of combination targeting of the PI3K/Akt pathway and the androgen-receptor axis in the clinic using AZD5363 and ENZ, respectively. [Read the Full Post]

Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR-independent pathway

514 | Mar 08 2019

Zhao X et al. demonstrated that compound C inhibited the phosphorylation of JNK and its target c-Jun. Blocking JNK by SP600125 or siRNA suppressed autophagy induction upon compound C treatment. Moreover, compound C induced p38 MAPK activation, and its inhibition promoted autophagy induction via JNK activation. In addition, compound C induced p53 expression, and its inhibition attenuated compound C-induced autophagic response. Thus, compound C triggers autophagy, at least in part, via the JNK and p53 pathways in human CCA cells. In conclusion, suppresses autophagy could increase compound C sensitivity in human CCA. [Read the Full Post]

In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors

543 | Mar 07 2019

Hao J et al. demonstrated the potential of zebrafish as an attractive complementary platform for drug development that incorporates an assessment of in vivo bioactivity and selectivity in the context of a living organism. [Read the Full Post]

The mTORC1/2 Inhibitor AZD8055 Strengthens the Efficiency of the MEK Inhibitor Trametinib to Reduce the Mcl-1/[Bim and Puma] ratio and to Sensitize Ovarian Carcinoma Cells to ABT-737

410 | Feb 19 2019

Pétigny-Lechartier C et al. indicated the three-drug combination was also very efficient when replacing AZD8055 by the pan-Akt inhibitor MK-2206. This study thus proposes original multitargeted strategies and may have important implications for the design of novel approaches for ovarian cancer treatment. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

541 | Feb 17 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128might be further investigated as a novel anti-OS agent. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

0 | Feb 17 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128might be further investigated as a novel anti-OS agent. [Read the Full Post]

Ionizing Radiation Blocks Hair Cell Regeneration in Zebrafish Lateral Line Neuromasts by Preventing Wnt Signaling

761 | Feb 15 2019

Li R et al. suggested that radiation suppressed hair cell regeneration in zebrafish lateral line neuromasts through inhibition of Wnt signaling in supporting cells possibly by secreting anti-proliferation factors like dkk2. Maintaining a healthy supporting cell pool is vital for regeneration of hair cells. [Read the Full Post]

Two mTOR inhibitors, rapamycin and Torin 1, differentially regulate iron-induced generation of mitochondrial ROS

707 | Feb 13 2019

Huang H et al. suggested that mTOR inhibition may not be able to alleviate iron-induced neurotoxicity. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

838 | Feb 01 2019

Hendriks CMM et al. suggested that the sulfilimidoyl- and sulfoximidoyl-substituted analogs are efficient ATR inhibitors. [Read the Full Post]

Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer

654 | Jan 30 2019

Qian J et al. found that the basal levels of carnitine palmitoyltransferase 1A and lipid catabolism were elevated in HER2+/PIK3CAmut breast cells and were inhibited upon mTOR-KI treatment. [Read the Full Post]

Synergistic antitumor effect of NVP-BEZ235 and CAPE on MDA-MB-231 breast cancer cells

704 | Jan 24 2019

Torki S et al. suggested that tumor metastasis and progression in TNBC cells can be effectively reduced through the concurrent use of NVP-BEZ235 and CAPE. This could be of particular interest in assessing the effects of this therapy in the reduction of tumor metastasis and progression in other tumor types. [Read the Full Post]

Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or dactolisib (BEZ235) in patients with castration-resistant prostate cancer

716 | Jan 24 2019

Massard C et al. indicated that based on the assessment of available pharmacokinetics, safety, and efficacy data, no further study is planned for either buparlisib or dactolisib in combination with AA in CRPC. [Read the Full Post]

A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening

991 | Jan 23 2019

Yan HHN et al. indicated this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy. [Read the Full Post]

Phase II Study of BEZ235 versus Everolimus in Patients with Mammalian Target of Rapamycin Inhibitor-Naïve Advanced Pancreatic Neuroendocrine Tumors

2472 | Jan 23 2019

Salazar R et al. showed thta BEZ235 treatment in mTOR inhibitor-naïve patients with advanced pNET did not demonstrate increased efficacy compared with everolimus and may be associated with a poorer tolerability profile. [Read the Full Post]

Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory-like CD8+ T cells for adoptive immunotherapy

0 | Jan 21 2019

Mousset CM et al. demonstrated that AKT-inhibitors with different modality of action promote the ex vivo generation of stem cell memory-like CD8+ T cells with a unique metabolic profile and retained polyfunctionality. Akt-inhibitor VIII and GDC-0068 outperformed other inhibitors, and are therefore promising candidates for ex vivo generation of superior tumor-reactive T cells for adoptive immunotherapy in cancer patients. [Read the Full Post]

A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer

876 | Jan 18 2019

Bang YJ et al. showed that Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed. [Read the Full Post]

Wortmannin-induced vacuole fusion enhances amyloplast dynamics in Arabidopsis zigzag1 hypocotyls

918 | Jan 14 2019

Alvarez AA et al. suggested that vacuole membrane remodeling may be involved in regulating the association of vacuoles and amyloplasts during graviperception. [Read the Full Post]

Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair

850 | Jan 01 2019

Lima M et al. identify ATR and ATM as central coordinators of the DDR to ecteinascidins and provide a mechanistic rationale for combining these compounds with ATR and ATM inhibitors. [Read the Full Post]

Enhanced efficacy of 5-fluorouracil in combination with a dual histone deacetylase and phosphatidylinositide 3-kinase inhibitor (CUDC-907) in colorectal cancer cells

1182 | Dec 26 2018

Hamam R et al. revealed, for the first time, the enhanced inhibitory effect of CUDC-907 against CRC cells when combined with 5-FU, supporting the application of this combination as a potential therapeutic strategy in CRC treatment. [Read the Full Post]

CUDC-907 Promotes Bone Marrow Adipocytic Differentiation Through Inhibition of Histone Deacetylase and Regulation of Cell Cycle

1351 | Dec 26 2018

Ali D et al. revealed that HDAC, PI3K, and cell cycle genes are important regulators of BMA formation and demonstrate that adipocyte differentiation of hBMSCs is associated with complex changes in a number of epigenetic and genetic pathways, which can be targeted to regulate BMA formation. [Read the Full Post]

Dual inhibition of PI3K and mTOR by VS-5584 suppresses thrombus formation

509 | Dec 19 2018

Später T et al. demonstrated that VS-5584 is a potent inhibitor of primary hemostasis targeting multiple platelet functions. [Read the Full Post]

Protease-activated receptor-2 promotes kidney tubular epithelial inflammation by inhibiting autophagy via the PI3K/Akt/mTOR signalling pathway

733 | Dec 18 2018

Du C et al. suggested that PAR2 inhibition may play a role in the treatment of diseases with increased inflammatory responses in renal systems. [Read the Full Post]

PI3Kδ and PI3Kγ isoforms have distinct functions in regulating pro-tumoural signalling in the multiple myeloma microenvironment

466 | Dec 14 2018

Piddock RE et al. reported that PI3Kδ and PI3Kγ isoforms have distinct functions in MM and that combined PI3kδ/γ isoform inhibition has anti-MM activity. Here we provide a scientific rationale for trials of dual PI3kδ/γ inhibition in patients with MM. [Read the Full Post]

Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells

812 | Dec 14 2018

Cheng L et al. found that TIC10 showed promising anti-HCC activity, alone or together with DNA-PKcs inhibitors. [Read the Full Post]

Regulatory Mechanisms Underlying the Expression of Prolactin Receptor in Chicken Granulosa Cells

572 | Dec 08 2018

Hu S et al. provided new insights into the regulatory mechanisms controlling the expression of PRLR in granulosa cells. [Read the Full Post]

AMPK activator acadesine fails to alleviate isoniazid-caused mitochondrial instability in HepG2 cells

686 | Dec 04 2018

Zhang TG et al. showed that AMPK activator acadesine (AICAR) alleviated INH-caused impairment of mitochondrial biogenesis by activation of silent information regulator two ortholog 1 (SIRT1)-peroxisome proliferator-activated receptor γ coactivator 1α (PGC1 α) pathway in HepG2 cells. [Read the Full Post]

Induction of galectin-1 by TLR-dependent PI3K activation enhances epithelial-mesenchymal transition of metastatic ovarian cancer cells

508 | Dec 03 2018

Park GB et al. demonstrated that TLR-mediated PI3K activation modulated the invasion and metastasis of ovarian cancer through the production of galectin-1, suggesting that inhibition of the p110 isoform is a promising therapeutic approach against metastatic ovarian cancer. [Read the Full Post]

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

769 | Dec 03 2018

Zhang Y et al. provided us with new insights regarding the mechanism by which p53 mediates A549 apoptosis and may cast light on the development of more efficient p53-based strategies for treating lung cancer. [Read the Full Post]

Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells

1171 | Nov 25 2018

Compagno M et al. showed that PI3Kδ or Bruton's tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. This effect should be carefully considered, as such inhibitors can be administered to patients for years. [Read the Full Post]

Identification of approved and investigational drugs that inhibit hypoxia-inducible factor-1 signaling

0 | Nov 17 2018

Hsu CW et al. underlined the importance of developing a battery of robust assay platforms and confirmation studies that focus on endogenous protein targets so that only relevant and reliable data will be taken into pre-clinical and clinical studies. [Read the Full Post]

Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells

481 | Nov 16 2018

Divac Rankov A et al. underlined the importance of testing autophagic activity of potential anticancer agents in a comparative approach to develop more rational anticancer therapeutic strategies. [Read the Full Post]

Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo

488 | Nov 13 2018

Wang L et al. demonstrated the potent anti-colon cancer cell activity by WYE-354, and its activity may be further augmented with autophagy inhibition. [Read the Full Post]

Stathmin decreases cholangiocarcinoma cell line sensitivity to staurosporine-triggered apoptosis via the induction of ERK and Akt signaling

772 | Nov 04 2018

Wang Y et al. indicated that understanding the regulation of anti-apoptosis effect by Stathmin might provide new insight into how to overcome therapeutic resistance in cholangiocarcinoma. [Read the Full Post]

Pro-survival signal inhibition by CDK inhibitor dinaciclib in Chronic Lymphocytic Leukaemia

1434 | Nov 01 2018

Chen Y et al. supported a therapeutic application of cyclin-dependent kinase inhibitors in CLL in combination with other relevant targeted therapies. [Read the Full Post]

Artesunate enhances the therapeutic response of glioma cells to temozolomide by inhibition of homologous recombination and senescence

899 | Oct 07 2018

Berte N et al. showed the amelioration of TMZ-induced cell death upon ART co-treatment provides a rational basis for a combination regime of TMZ and ART in glioblastoma therapy. [Read the Full Post]

Novel role of STRAP in progression and metastasis of colorectal cancer through Wnt/β-catenin signaling

0 | Oct 06 2018

Yuan G et al. suggest that STRAP increases invasion and metastasis of CRC partly through inhibiting ubiquitin-dependent degradation of β-catenin and promoting Wnt/β-catenin signaling. [Read the Full Post]

ATM induces MacroD2 nuclear export upon DNA damage

1516 | Oct 03 2018

Golia B et al. identified a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. [Read the Full Post]

TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2

500 | Oct 02 2018

Venkatesan S et al. suggested that Bcl-2 confers resistance to mTORC1/2 inhibitors in TP53 wild type GSCs and that combined inhibition of both mTORC1/2 and Bcl-2 is worthwhile to explore further in TP53 wild type glioblastomas, whereas in TP53 mutated glioblastomas dual mTORC1/2 inhibitors should be explored. [Read the Full Post]

Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism

907 | Sep 23 2018

Rahmani M et al. argued that combining PI3K/AKT/mTOR inhibitors with BH3 mimetics warrants attention in AML, particularly in the setting of basal AKT activation and/or addiction. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

0 | Sep 17 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

PI3Kδ and PI3Kγ isoforms have distinct functions in regulating pro-tumoural signalling in the multiple myeloma microenvironment

1630 | Sep 16 2018

Piddock RE et al. provided a scientific rationale for trials of dual PI3kδ/γ inhibition in patients with MM. [Read the Full Post]

Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin

0 | Sep 12 2018

Jan WC et al. confirmed that PI3K, especially the isoforms of PI3Kβ, PI3Kδ, and PI3Kγ, is involved in mediating the anti-inflammatory effects of vasopressin. [Read the Full Post]

ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis

1641 | Sep 04 2018

Aragoneses-Fenoll L et al. showed that p110α as well as p110δ Class IA PI3Ks are important to immune regulation; inhibition of both subunits may be an effective therapeutic approach in inflammatory autoimmune diseases like rheumatoid arthritis. [Read the Full Post]

The E545K mutation of PIK3CA promotes gallbladder carcinoma progression through enhanced binding to EGFR

0 | Sep 04 2018

Zhao S et al. indicated that the prognoses of patients with E545K mutation were worse than patients without this mutation. The E545K mutation promoted GBC progression through enhanced binding to EGFR and activating downstream akt activity. The PI3K selective inhibitor, A66, suppressed gallbladder carcinoma proliferation. [Read the Full Post]

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

0 | Sep 03 2018

Pu Y et al. suggested that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8. [Read the Full Post]

PIM kinases as therapeutic targets against advanced melanoma

593 | Aug 28 2018

Shannan B et al. suggested that PIM inhibitors provide promising additions to the targeted therapies available to melanoma patients. [Read the Full Post]

INPP4B and PTEN Loss Leads to PI-3,4-P2 Accumulation and Inhibition of PI3K in TNBC

650 | Aug 28 2018

Reed DE et al. supported a model where PI-3,4-P2 is inhibitory toward PI3K, revealing a novel feedback mechanism under conditions of excessive signaling, and potentially an indication for PI3K-β isoform-specific inhibitors in PTEN-null TNBC that have lost INPP4B expression. [Read the Full Post]

Activation of IGF1R/p110β/AKT/mTOR confers resistance to α-specific PI3K inhibition

0 | Aug 27 2018

Leroy C et al. demonstrates that the IGF1R/p110β/AKT/mTOR axis confers resistance to BYL719 in PIK3CA mutant breast cancers. This provides a rationale for the combined targeting of p110α with IGF1R or p110β in patients with breast tumors harboring PIK3CA mutations. [Read the Full Post]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

2473 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer Cells

1452 | Aug 22 2018

Luo LX et al. indicated these results broaden our understanding of the mechanisms on honokiol effects in lung cancer, and reinforce the possibility of its potential anticancer benefit as a popular Chinese herbal medicine (CHM). [Read the Full Post]

Combined Inhibition of Both p110α and p110β Isoforms of Phosphatidylinositol 3-Kinase Is Required for Sustained Therapeutic Effect in PTEN-Deficient, ER+ Breast Cancer

0 | Aug 21 2018

Hosford SR et al. indicated that p110β is the dominant PI3K isoform in PTEN-deficient, ER+ breast cancer cells. Upon p110β inhibition, p110α did not induce significant reactivation of AKT, but combined targeting of p110α/β most effectively induced apoptosis in vitro and in vivo and provided durable tumor regression. Because apoptosis and tumor regression occurred early but not late in the treatment course, and proliferative arrest was maintained throughout treatment, p110α/β inhibitors may be considered short-term cytotoxic agents and long-term cytostatic agents. [Read the Full Post]

Discovery and Characterization of Novel GPR39 Agonists Allosterically Modulated by Zinc

615 | Aug 21 2018

Sato S et al. revealed an unexpected role of zinc as an allosteric potentiator of small-molecule-induced activation of GPR39 and expand the list of potential kinase off-targets to include understudied G protein-coupled receptors. [Read the Full Post]

Ridaforolimus improves the anti-tumor activity of dual HER2 blockade in uterine serous carcinoma in vivo models with HER2 gene amplification and PIK3CA mutation

657 | Aug 20 2018

Hernandez SF et al. suggested that PIK3CA gene mutation may be an effective biomarker for selecting those HER2 over-expressing USC tumors most likely to benefit from mTOR inhibition. [Read the Full Post]

Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors

660 | Jul 30 2018

Vandamme T et al. indicated that long-term everolimus resistance was induced in two human PNET cell lines. Novel PI3K-AKT-mTOR pathway-targeting drugs can overcome everolimus resistance. Differential gene expression profiles suggest different mechanisms of everolimus resistance in BON-1 and QGP-1. [Read the Full Post]

Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors

662 | Jul 30 2018

Jin HO et al. suggested that combining mTORC1/2 inhibitors with inhibitors of JNK or autophagy might be an effective approach for improving therapeutic outcomes in NSCLC. [Read the Full Post]

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells

1241 | Jul 29 2018

Zhen MC et al. showed that AT406 induced degradation of IAPs (cIAP-1 and XIAP), but didn't affect another anti-apoptosis protein Mcl-1. Co-treatment of OSI-027 caused simultaneous Mcl-1 downregulation to overcome AT406's resistance. Significantly, shRNA knockdown of Mcl-1 remarkably facilitated AT406-induced apoptosis in HCC cells. In vivo, AT406 oral administration suppressed HepG2 tumor growth in nude mice. Its activity was potentiated with co-administration of OSI-027. We conclude that mTOR could be a key resistance factor of AT406 in HCC cells. [Read the Full Post]

GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines

809 | Jul 28 2018

Durbas M et al. extended knowledge on mechanisms of action of the 14G2a mAb on the neuroblastoma cells. [Read the Full Post]

GSK621 Targets Glioma Cells via Activating AMP-Activated Protein Kinase Signalings

778 | Jul 26 2018

Jiang H et al. summarized that GSK621 inhibits human glioma cells possibly via activating AMPK signaling. This novel AMPK activator could be a novel and promising anti-glioma cell agent. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

0 | Jul 23 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study

1148 | Jul 17 2018

Feng Y et al. demonstrated the potent anti-lung cancer activity by ONC201. [Read the Full Post]

Selective Sparing of Human Tregs by Pharmacologic Inhibitors of the Phosphatidylinositol 3-Kinase and MEK Pathways

596 | Jul 16 2018

Zwang NA et al. suggested less functional reliance on PI3K and MEK signaling in Tregs compared with conventional CD4(+) and CD8(+) lymphocytes. Therefore, the PI3K and MEK pathways are attractive pharmacologic targets for transplantation and treatment of autoimmunity. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

0 | Jul 15 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Role and mechanism of PTEN in adiponectin-induced osteogenesis in human bone marrow mesenchymal stem cells

850 | Jul 11 2018

Liu X et al. suggested that APN enhanced osteogenic differentiation of hBMSCs in vitro partially by inhibiting PTEN expression. APN could be a therapeutic agent in tissue regeneration engineering and bone regeneration by inhibiting PTEN expression and then promoting the osteogenic differentiation of hBMSCs. [Read the Full Post]

The afatinib resistance of in vivo generated H1975 lung cancer cell clones is mediated by SRC/ERBB3/c-KIT/c-MET compensatory survival signaling

1382 | Jul 11 2018

Booth L et al. showed the inhibition of ERBB3 signaling via both blockade of SRC and ERBB1 results in tumor cell death. [Read the Full Post]

Activation of IGF1R/p110β/AKT/mTOR confers resistance to α-specific PI3K inhibition

2690 | Jul 08 2018

Leroy C, et al. demonstrated that the IGF1R/p110β/AKT/mTOR axis confers resistance to BYL719 in PIK3CA mutant breast cancers. This provides a rationale for the combined targeting of p110α with IGF1R or p110β in patients with breast tumors harboring PIK3CA mutations. [Read the Full Post]

PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors

1994 | Jul 08 2018

Yahiaoui A et al. described both the additive interaction of and resistance mechanisms to idelalisib and ONO/GS-4059 in a model of activated B-cell-like diffuse large B-cell lymphoma. [Read the Full Post]

Combination treatment for myeloproliferative neoplasms using JAK and pan-class I PI3K inhibitors

690 | Jul 07 2018

Choong ML et al. supported the use of a combination of JAK2 and pan-class I PI3K inhibitors in the treatment of MPNs. [Read the Full Post]

RAD51 inhibition in triple negative breast cancer cells is challenged by compensatory survival signaling and requires rational combination therapy

1110 | Jul 05 2018

Wiegmans AP et al. highlight a potential compensatory mechanism via p38 that limits DNA targeted therapy. [Read the Full Post]

Adenovirus-mediated TIPE2 overexpression inhibits gastric cancer metastasis via reversal of epithelial-mesenchymal transition

1191 | Jun 25 2018

Yin H et al. provided the first evidence that TIPE2 inhibits gastric cancer cell migration, invasion and metastasis very probably via reversal of EMT, revealing that TIPE2 may be a novel therapeutic target for human gastric cancer EMT and metastasis. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

3442 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin

1246 | Jun 07 2018

Jan WC et al. confirmed that PI3K, especially the isoforms of PI3Kβ, PI3Kδ, and PI3Kγ, is involved in mediating the anti-inflammatory effects of vasopressin. [Read the Full Post]

Serine/Threonine Kinase Unc-51-like Kinase-1 (Ulk1) Phosphorylates the Co-chaperone Cell Division Cycle Protein 37 (Cdc37) and Thereby Disrupts the Stability of Cdc37 Client Proteins

1055 | Jun 01 2018

Li R et al. provided evidence for an anti-proliferative role of Ulk1 in response to Hsp90 inhibition in cancer cells. [Read the Full Post]

Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

1095 | May 29 2018

Yang LY et al. concluded that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. [Read the Full Post]

Novel Akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head

0 | May 27 2018

Chen YX et al. proposed that SC-79 treatment to rescue Akt activation could be tested in the clinic as a potential therapeutic approach to preventing the development of alcohol-induced ONFH. [Read the Full Post]

SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

998 | May 27 2018

Gong YQ et al. suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis. [Read the Full Post]

Enhanced efficacy of combined HDAC and PARP targeting in glioblastoma

1142 | May 25 2018

Rasmussen RD et al. provided a pre-clinical rationale for combined administration of SAHA and olaparib, which are already individually in clinical trials. [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

1812 | May 21 2018

Franks SE et al. suggested that compounds selectively targeting AKT1 may prove more effective than compounds that inhibit all three AKT isoforms at least in the treatment of lung adenocarcinoma. [Read the Full Post]

Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells

1245 | May 20 2018

Ma J et al. provided insight into the mechanism of action underlying the synergistic antileukemic activity of ATR inhibition in combination with cytarabine in AML. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

6155 | May 20 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

VS-5584, a Novel PI3K-mTOR Dual Inhibitor, Inhibits Melanoma Cell Growth In Vitro and In Vivo

674 | May 15 2018

Shao Z et al. provided the rationale for the clinical assessment of VS-5584 in melanoma patients and development of ABT-737 and other Bcl-xL/Bcl-2 inhibitors as the possible adjuvants. [Read the Full Post]

Identification of TG100-115 as a new and potent TRPM7 kinase inhibitor, which suppresses breast cancer cell migration and invasion

728 | May 10 2018

Song C et al. indicated that TG100-115 can be used as a potent TRPM7 kinase inhibitor and a potent inhibitor of breast cancer cell migration. [Read the Full Post]

Co-occurring Mutations of Tumor Suppressor Genes, LATS2 and NF2, in Malignant Pleural Mesothelioma

1181 | May 05 2018

Tranchant R et al. identified a new MPM molecular subgroup that shares common genetic and transcriptomic characteristics. Our results made it possible to highlight a greater sensitivity to an anticancer compound for this MPM subgroup and to identify a specific potential biomarker. [Read the Full Post]

FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation

3139 | May 03 2018

Zhao H et al. indicated that FGFR4/GSK3β/β-catenin axis may play a pivotal role in FGF19-induced EMT in HCC cells. As FGF19 and its specific receptor FGFR4 are frequently amplified in HCC cells, selective targeting this signaling node may lend insights into a potential effective therapeutic approach for blocking metastasis of HCC. [Read the Full Post]

GSK3ß-dependent dysregulation of neurodevelopment in SPG11-patient iPSC model

3297 | May 02 2018

Mishra HK et al. provided the first evidence for an early neurodevelopmental phenotype in SPG11, with GSK3ß as a potential novel target to reverse the disease phenotype. This article is protected by copyright. All rights reserved. [Read the Full Post]

UCN-01 enhances cytotoxicity of irinotecan in colorectal cancer stem-like cells by impairing DNA damage response

1034 | Apr 19 2018

Signore M et al. showed that combination of LY2603618, a specific Chk1/2 inhibitor, with irinotecan resulted in a significant reduction of CRC-SC growth in vivo, confirming that irinotecan treatment coupled to inhibition of Chk1 represents a potentially effective therapeutic approach for CRC treatment. [Read the Full Post]

Inhibition of autophagy enhances effects of PF-04691502 on apoptosis and DNA damage of lung cancer cells

2105 | Apr 14 2018

Fei HR et al. suggested that a strategy of blocking autophagy to enhance the activity of PI3K/mTOR inhibitors warrants further attention in treatment of NSCLC cells. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

0 | Apr 11 2018

Simioni C et al. indicated that either single or combined administration of drugs against the different targets displayed inhibition of cellular viability associated with a concentration-dependent induction of apoptosis, cell cycle arrest in G0/G1 phase and autophagy, having the combined treatments a significant synergistic cytotoxic effect. Co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

FcγRIIB-Independent Mechanisms Controlling Membrane Localization of the Inhibitory Phosphatase SHIP in Human B Cells

2604 | Apr 10 2018

Pauls SD et al. indicated that FcγRIIB is not uniquely able to promote membrane recruitment of SHIP, but rather modulates its function via formation of distinct signaling complexes. Membrane recruitment of SHIP via Syk-dependent mechanisms may be an important factor modulating immunoreceptor signaling. [Read the Full Post]

Novel Akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head

1802 | Apr 09 2018

Chen YX et al. showed that alcohol-induced ONFH is associated with suppression of p-Akt-Ser473 in the Akt/GSK3β/β-catenin signaling pathway in bone mesenchymal stem cells. We propose that SC-79 treatment to rescue Akt activation could be tested in the clinic as a potential therapeutic approach to preventing the development of alcohol-induced ONFH. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

0 | Apr 07 2018

Simioni C et al. found that co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Retinoic acid promotes expression of germline-specific genes in chicken blastoderm cells by stimulating Smad1/5 phosphorylation in a feeder-free culture system

0 | Mar 30 2018

Tang X et al. demonstrated that E8 medium is able to maintain cBC growth for weeks and RA treatment induced germ cell differentiation of cBCs through the BMP-Smad1/5 signaling pathway. [Read the Full Post]

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

1125 | Mar 20 2018

Chen X et al. revealed a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. [Read the Full Post]

CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma

1100 | Mar 20 2018

Mohanty A et al. uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL. [Read the Full Post]

Nevospheres from neurocutaneous melanocytosis cells show reduced viability when treated with specific inhibitors of NRAS signaling pathway

702 | Mar 19 2018

Basu D et al. indicated NRAS mutated cells derived from clinical NCM samples are capable of continuous growth as spheroid colonies in vitro and retain their genetic identity. Drugs targeting the NRAS signaling pathway reduce in vitro viability of NCM cells. NCM lesional spheroids represent a new and reliable experimental model of NCM for use in drug testing and mechanistic studies. [Read the Full Post]

Activation of the PI3K/mTOR Pathway following PARP Inhibition in Small Cell Lung Cancer

1142 | Mar 09 2018

Cardnell RJ et al. suggested that combining PARP and PI3K inhibitors enhances the effect of either agent alone in preclinical models of SCLC, warranting further investigation of such combinations in SCLC patients. [Read the Full Post]

Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer

1168 | Mar 08 2018

Bhattacharya B et al. showed that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

0 | Mar 04 2018

Wu J, et al. indicated AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

1194 | Mar 02 2018

Wu J et al. found that AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

Effective combinatorial immunotherapy for castration-resistant prostate cancer

1717 | Feb 21 2018

Xin Lu et al. illuminated a clinical path hypothesis for combining immune checkpoint blockade with MDSC-targeted therapies in the treatment of mCRPC. [Read the Full Post]

A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

2048 | Feb 17 2018

Zhang Q et al. showed a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay. [Read the Full Post]

The PI3K/Akt/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells

1661 | Feb 09 2018

Chang H et al. suggested that the PI3K/Akt/mTOR signaling pathway participates in the process of autophagy induced by CVB3 infection. This finding may provide a new perspective of CVB3-induced autophagy. [Read the Full Post]

Identification of TG100-115 as a new and potent TRPM7 kinase inhibitor, which suppresses breast cancer cell migration and invasion

702 | Feb 08 2018

Song C, et al. found that TG100-115 can be used as a potent TRPM7 kinase inhibitor and a potent inhibitor of breast cancer cell migration. [Read the Full Post]

Fibroblast Growth Factor 21 (FGF21) Promotes Formation of Aerobic Myofibers via the FGF21-SIRT1-AMPK-PGC1α Pathway

827 | Feb 07 2018

Liu X et al. revealed a novel mechanism of myogenesis and muscle fiber transformation and indicated that FGF21 serves as a vital regulator of muscle development and important contributor to the pathogenesis of myopathy. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

0 | Jan 31 2018

Tong J et al. demonstrated FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

ART3 regulates triple-negative breast cancer cell function via activation of Akt and ERK pathways

1473 | Jan 30 2018

Tan L et al. showed that ART 3 overexpression activated AKT and ERK in vitro and in xenograft tumors. Together, our findings demonstrate that ART3 is a critical TNBC marker with functional significance. [Read the Full Post]

Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer

1284 | Jan 29 2018

Ahmad R et al. indicated that MUC1-C is a potential target for the treatment of colorectal cancer. Colorectal cancer patients who overexpress MUC1-C may be candidates for treatment with the MUC1-C inhibitor alone or in combination therapy with other agents. [Read the Full Post]

MFN2 suppresses cancer progression through inhibition of mTORC2/Akt signaling

718 | Jan 25 2018

Xu K et al. provided novel insights into the tumor progression associated with MFN2 deficiency and suggests that the importance of mTORC2 inhibitor in the treatment of MFN2 downregulated cancer patients. [Read the Full Post]

Targeting DNA repair with aphidicolin sensitizes primary chronic lymphocytic leukemia cells to purine analogs

1576 | Jan 19 2018

Starczewska E et al. indicated that aphidicolin potentiates the cytotoxicity of purine analogs by inhibiting a DNA repair pathway that involves DNA polymerases, most likely NER, and provide a rationale for manipulating it to therapeutic advantage. [Read the Full Post]

Development of novel PET probes targeting phosphatidylinositol 3-kinase (PI3K) in tumors

1245 | Jan 18 2018

Makino A et al. represented the first trial of a PET tracer for detecting PI3K. Although further improvement of the probe is required prior to clinical application, these results should encourage future work. [Read the Full Post]

DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP

1203 | Jan 18 2018

Mimmler M et al. supported the notion that ATR plays a key role in the defense against cancer formation induced by PhIP and related HCAs. [Read the Full Post]

mTOR inhibition sensitizes human hepatocellular carcinoma cells to resminostat

0 | Jan 17 2018

Peng X et al. suggested that mTOR could be a primary resistance factor of resminostat. Targeted inhibition of mTOR may thus significantly sensitize HCC cells to resminostat. [Read the Full Post]

Epigenetic silencing of miR-137 induces drug resistance and chromosomal instability by targeting AURKA in multiple myeloma

1710 | Jan 09 2018

Qin Y et al. demonstrated that miR-137 is epigenetically silenced in MM, and overexpression of miR-137 could reduce drug resistance and overcome chromosomal instability of the MM cells via affecting the apoptosis and DNA damage pathways. [Read the Full Post]

Development of a test that measures real-time HER2 signaling function in live breast cancer cell lines and primary cells

921 | Jan 04 2018

Measurement of HER2 signaling activity in the tumor cells of breast cancer patients is a feasible approach to explore as a biomarker to identify HER2-driven cancers not currently diagnosable with genomic techniques. [Read the Full Post]

Insulin receptor substrate 1 is a substrate of the Pim protein kinases

1232 | Jan 03 2018

Song JH et al. demonstrated that IRS1S1101 is a novel substrate for the Pim kinases and provide a novel marker for evaluation of Pim inhibitor therapy. [Read the Full Post]

Noninvasive Bioluminescence Imaging of AKT Kinase Activity in Subcutaneous and Orthotopic NSCLC Xenografts: Correlation of AKT Activity with Tumor Growth Kinetics

1118 | Jan 01 2018

Suchowski K et al. demonstrated that BAR can be applied to study drug dosing, drug combinations, and treatment efficacy in orthotopic mouse lung tumor models. [Read the Full Post]

MEK-ERK inhibition potentiates WAY-600-induced anti-cancer efficiency in preclinical hepatocellular carcinoma (HCC) models

1599 | Dec 30 2017

Wang K et al. demonstrated the potent anti-HCC activity by WAY-600, either alone or with MEK-ERK inhibitors. [Read the Full Post]

Role of reactive oxygen species-mediated MAPK and NF-κB activation in polygonatum cyrtonema lectin-induced apoptosis and autophagy in human lung adenocarcinoma A549 cells

1694 | Dec 30 2017

Liu T et al. provided a new perspective of PCL as a potential anti-tumour drug targeting apoptosis and autophagy pathways for future cancer therapeutics. [Read the Full Post]

ZSTK474, a specific class I phosphatidylinositol 3-kinase inhibitor, induces G1 arrest and autophagy in human breast cancer MCF-7 cells

838 | Dec 25 2017

Wang Y et al. supported the application of ZSTK474, which is being evaluated in clinical trials, for breast cancer therapy. [Read the Full Post]

DNA Damage Response in Human Stem Cells and Neural Descendants

1224 | Dec 23 2017

Wei J et al. demonstrated that these processes exhibit spatiotemporal evolution during cell differentiation. [Read the Full Post]

Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

1245 | Dec 21 2017

You M et al. provide molecular insight into the mechanism of IFN-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment. [Read the Full Post]

Vascular CXCR4 Expression Promotes Vessel Sprouting and Sensitivity to Sorafenib Treatment in Hepatocellular Carcinoma

1206 | Dec 20 2017

Xu J et al. revealed that CXCR4 is a novel HCC vascular marker for vessel sprouting and could serve as a potential therapeutic target and a predictive factor for sorafenib treatment in patients with HCC. [Read the Full Post]

PKCiota promotes ovarian tumor progression through deregulation of cyclin E

1859 | Dec 19 2017

Nanos-Webb A et al. identified a PI3K/PKCiota/cyclin E signaling pathway as a therapeutic target during ovarian tumorigenesis. [Read the Full Post]

Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo

1262 | Dec 18 2017

Shen J et al. supported the feasibility of further investigation of the perifosine plus ABT-737 regimen in future lung cancer clinical tests. [Read the Full Post]

Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma

1235 | Dec 17 2017

Gu X et al. details the impact of perifosine on proteome and lysine acetylome in SK-N-AS cells and expands our understanding of the mechanisms of perifosine action in neuroblastoma. [Read the Full Post]

Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells

1247 | Dec 17 2017

Ma J et al. provided insight into the mechanism of action underlying the synergistic antileukemic activity of ATR inhibition in combination with cytarabine in AML. [Read the Full Post]

Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma

1676 | Dec 08 2017

Combined inhibition of AKT and BTK, PIM2, or S6K1 proved to be an effective strategy to overcome resistance to AKT inhibition in DLBCL. [Read the Full Post]

Optogenetic clustering of CNK1 reveals mechanistic insights in RAF and AKT signalling controlling cell fate decisions

1505 | Dec 08 2017

Fischer A et al. found that CNK1 expression, CNK1 clustering and the thereto related differential signalling processes decide on proliferation and differentiation in a cell type- and cell stage-dependent manner by orchestrating AKT and RAF signalling. [Read the Full Post]

Autophagy prevention sensitizes AKTi-1/2-induced anti-hepatocellular carcinoma cell activity in vitro and in vivo

0 | Nov 30 2017

Zhang Q et al. demonstrated that autophagy activation serves as a main resistance factor of AKTi-1/2 in HCC cells. Autophagy prevention therefore sensitizes AKTi-1/2-induced anti-HCC activity in vitro and in vivo. [Read the Full Post]

Autophagy prevention sensitizes AKTi-1/2-induced anti-hepatocellular carcinoma cell activity in vitro and in vivo

1180 | Nov 29 2017

Zhang Q et al. demonstrate that autophagy activation serves as a main resistance factor of AKTi-1/2 in HCC cells. [Read the Full Post]

Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase 3-mediated phosphorylation and degradation of interleukin-17 receptor

1069 | Nov 23 2017

Liu S et al.revealed a mechanism underlying the intensified inflammation in obesity and obesity-associated development of aggressive prostate cancer, suggesting that targeting GSK3 may be a potential therapeutic approach to suppress IL-17-mediated inflammation in the prevention and treatment of prostate cancer, particularly in obese men. [Read the Full Post]

Retinoic acid promotes expression of germline-specific genes in chicken blastoderm cells by stimulating Smad1/5 phosphorylation in a feeder-free culture system

1050 | Nov 12 2017

Tang X et al. demonstrated that E8 medium is able to maintain cBC growth for weeks and RA treatment induced germ cell differentiation of cBCs through the BMP-Smad1/5 signaling pathway. [Read the Full Post]

Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity

0 | Oct 31 2017

Lee MJ, et al. demonstrated that PI3Kδ regulates Dectin-2 signaling and its dendritic cell function. [Read the Full Post]

MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated

1520 | Oct 26 2017

Smida M et al. showed that ATM mutational status in lung cancer is a mechanistic biomarker for MEK inhibitor response, which may improve patient stratification and extend the applicability of these drugs beyond RAS and BRAF mutant tumours. [Read the Full Post]

PI3K Inhibitors Synergize with FGFR Inhibitors to Enhance Antitumor Responses in FGFR2mutant Endometrial Cancers

0 | Oct 24 2017

Packer L et al. provided evidence that subtherapeutic doses of PI3K inhibitors enhance the efficacy of anti-FGFR therapies, and a combination therapy may represent a superior therapeutic treatment in patients with FGFR2mutant endometrial cancer. [Read the Full Post]

Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo

1363 | Sep 17 2017

Wang H et al. found that erianin may be a promising agent for anticancer therapy against OS. [Read the Full Post]

Serpine2, a potential novel target for combating melanoma metastasis

0 | Sep 15 2017

Wu QW et al. suggested a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. [Read the Full Post]

Autophagy induction contributes to GDC-0349 resistance in head and neck squamous cell carcinoma (HNSCC) cells

0 | Sep 08 2017

Zhou Y et al. provided evidences to support GDC-0349 as a promising anti-HNSCC agent. [Read the Full Post]

Liraglutide attenuates the osteoblastic differentiation of MC3T3‑E1 cells by modulating AMPK/mTOR signaling

3884 | Aug 27 2017

Hu XK et al. study demonstrate that liraglutide attenuates osteoblastic differentiation of MC3T3‑E1 cells via modulation of AMPK/mTOR signaling. The present study revealed a novel function of liraglutide, which contributes to the understanding of its pharmacological and physiological effects in clinical settings. [Read the Full Post]

miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

0 | Aug 25 2017

Zhang W et al. demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. [Read the Full Post]

Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway

0 | Aug 25 2017

Ming GF et al. suggested that the treatment of EPCs with visfatin markedly attenuates the ox-LDL-induced senescence of EPCs by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway. [Read the Full Post]

Differential compensation mechanisms define resistance to PI3K inhibitors in PIK3CA amplified HNSCC

935 | Aug 24 2017

Michmerhuizen NL et al. suggestED that inhibition of the PI3K and Ras-MEK-ERK pathways might be effective in some HNSCC patients; however, it also prompts the study of additional resistance mechanisms to identify synergistic combination therapies for tumors resistant to these di-therapies. [Read the Full Post]

Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition

1136 | Aug 22 2017

Sano O et al. concluded that PIKfyve inhibitors are novel chemical tools for regulating autophagy. [Read the Full Post]

Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage

0 | Aug 19 2017

Finzel A et al. revealed a new regulatory interplay in which loss of DNA-PKcs function leads to hyperactivation of ATM and amplification of the p53 response, sensitizing cells for damage-induced senescence. [Read the Full Post]

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

0 | Aug 19 2017

Acharya S et al. indicated that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. [Read the Full Post]

Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin

1051 | Aug 13 2017

Wu J et al. indicated that TCTP might be suitable as a biomarker and that combinatorial treatment using 5-FU/oxaliplatin, together with mTOR kinase inhibitors, could be a route to preventing the development of resistance to these drugs. [Read the Full Post]

mTOR inhibition sensitizes human hepatocellular carcinoma cells to resminostat.

0 | Aug 12 2017

Peng X et al. suggested that mTOR could be a primary resistance factor of resminostat. [Read the Full Post]

PI3K Inhibitors Synergize with FGFR Inhibitors to Enhance Antitumor Responses in FGFR2mutant Endometrial Cancers

0 | Aug 10 2017

Packer L et al. provided evidence that subtherapeutic doses of PI3K inhibitors enhance the efficacy of anti-FGFR therapies, and a combination therapy may represent a superior therapeutic treatment in patients with FGFR2mutant endometrial cancer. [Read the Full Post]

Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development

973 | Aug 06 2017

Herrero-Sánchez MC et al. support the use of PI3K inhibitors to control T cell responses and show the potential utility of the dual PI3K/mTOR inhibitor BEZ235 in GvHD prophylaxis. [Read the Full Post]

Exogenous HGF Prevents Cardiomyocytes from Apoptosis after Hypoxia via Up-Regulating Cell Autophagy

0 | Aug 05 2017

Wang Y et al. revealed a potential mechanism in which exogenous HGF prevented NRVMs from apoptosis after hypoxia. [Read the Full Post]

PI3K Inhibitors Synergize with FGFR Inhibitors to Enhance Antitumor Responses in FGFR2mutant Endometrial Cancers

1018 | Aug 03 2017

Packer L et al. provided evidence that subtherapeutic doses of PI3K inhibitors enhance the efficacy of anti-FGFR therapies, and a combination therapy may represent a superior therapeutic treatment in patients with FGFR2mutant endometrial cancer. [Read the Full Post]

Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin.

0 | Jul 22 2017

Tao L et al. provided insight into how xanthatin and related molecules could be effectively targeted toward certain tumors. [Read the Full Post]

Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells

1196 | Jul 17 2017

Katsha A et al. indicated that AURKA plays an important role in the activation of EIF4E and cap-dependent translation. Targeting the AURKA-EIF4E-c-MYC axis using alisertib is a novel therapeutic strategy that can be applicable for everolimus-resistant tumors and/or subgroups of cancers that show overexpression of AURKA and activation of EIF4E and c-MYC. [Read the Full Post]

WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

0 | Jul 14 2017

Lu S et al. demonstrated that Akt signaling pathway mediates WISP1-induced migration and proliferation of human VSMCs, suggesting that WISP1 may act as a novel potential therapeutic target for vascular restenosis. [Read the Full Post]

Tris (1, 3-dichloro-2-propyl) phosphate induces apoptosis and autophagy in SH-SY5Y cells: Involvement of ROS-mediated AMPK/mTOR/ULK1 pathways

1578 | Jul 12 2017

Li R et al. provided the first evidence that TDCIPP promotes apoptosis and autophagy simultaneously and that this process involves the ROS-mediated AMPK/mTOR/ULK1 pathways. Lastly, the induction of autophagy is a protective mechanism against TDCIPP-induced apoptosis. [Read the Full Post]

Manganese-Stimulated Kisspeptin Is Mediated by the IGF-1/Akt/Mammalian Target of Rapamycin Pathway in the Prepubertal Female Rat

0 | Jul 11 2017

Srivastava VK et al. suggested that Mn acts, at least in part, through the IGF-1/Akt/mTOR pathway to influence prepubertal kisspeptin and LHRH. [Read the Full Post]

WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression.

0 | Jul 08 2017

Cai T et al. suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT/β-catenin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC. [Read the Full Post]

Inhibition of mTOR Signaling Pathway Delays Follicle Formation in Mice

0 | Jul 08 2017

Zhang J et al. suggested that KITL functions downstream of mTOR in somatic cells to regulate their communication with oocytes during follicle formation. [Read the Full Post]

Suppression of Virulent Porcine Epidemic Diarrhea Virus Proliferation by the PI3K/Akt/GSK-3α/β Pathway

4036 | Jul 04 2017

Kong N et al. suggested that PI3K/Akt/GSK-3α/β signaling pathway is activated by PEDV and functions in inhibiting PEDV replication. [Read the Full Post]

Generation of Cardiomyocytes from Pluripotent Stem Cells

1678 | Jul 03 2017

Nakahama H et al. described two different methods for acquiring CMs from human pluripotent lines. One method involves the generation of embryoid bodies, which emulates the natural developmental process, while the other method chemically activates the canonical Wnt signaling pathway to induce a monolayer of cardiac differentiation. [Read the Full Post]

Role of Wnt/β-catenin, Wnt/c-Jun N-terminal kinase and Wnt/Ca2+ pathways in cisplatin-induced chemoresistance in ovarian cancer

3943 | Jul 03 2017

Huang L et al. indicated that β-catenin, JNK and CaMKII are potential therapeutic targets in chemoresistant ovarian cancers. [Read the Full Post]

Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer

2155 | Jun 27 2017

Massihnia D et al. found that inhibition of Glut1 might overcome resistance to these therapies and warrants further studies. [Read the Full Post]

Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes

2355 | Jun 25 2017

Liu DD et al. suggested that the reduction of lipids accumulation induced-by inhibiting PI3K-Akt-mTOR pathway was closely linked to the decrease of lipogenesis, the increase of fatty acids oxidation, and the increase of VLDL assembly and secretion in goose hepatocytes. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

3733 | Jun 25 2017

The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. [Read the Full Post]

A role of KIT receptor signaling for proliferation and differentiation of rat stem Leydig cells in vitro

2782 | Jun 15 2017

Liu S et al. found KITL is a growth factor that regulates the development of the stem Leydig cell. [Read the Full Post]

Analysis of Endogenous Protein Interactions of Polycomb Group of Proteins in Mouse Embryonic Stem Cells.

2692 | Jun 14 2017

Morey L et al. described several methods to study Polycomb architecture, and identification of novel interactors in both pluripotent and differentiating mouse embryonic stem cells. [Read the Full Post]

Combretastatin A-1 phosphate, a microtubule inhibitor, acts on both hepatocellular carcinoma cells and tumor-associated macrophages by inhibiting the Wnt/β-catenin pathway

1546 | Jun 09 2017

Mao J et al. indicated that CA1P has great potential to impact both cancer cells and the microenvironment. [Read the Full Post]

AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication

0 | Jun 02 2017

Booth L et al. had demonstrated that AR-12 (OSU-03012) reduces the function and ATPase activities of multiple HSP90 and HSP70 family chaperones. [Read the Full Post]

Defects in dermal Vγ4 γ δ T cells result in delayed wound healing in diabetic mice

1868 | May 31 2017

Liu Z et al. found that defects in dermal Vγ4 γ δ T cells may be an important mechanism underlying delayed wound healing in diabetic mice. [Read the Full Post]

Phosphorylated heat shock protein 27 promotes lipid clearance in hepatic cells through interacting with STAT3 and activating autophagy

0 | May 25 2017

Shen L et al. provided a novel mechanism by which the phosphorylated Hsp27 promotes hepatic lipid clearance and suggests a new insight for therapy of steatotic diseases such as nonalcoholic fatty liver disease (NAFLD). [Read the Full Post]

PI3K p110β isoform synergizes with JNK in the regulation of glioblastoma cell proliferation and migration through Akt and FAK inhibition

2439 | May 24 2017

Zhao HF et al. suggested that combined inhibition of PI3K p110β isoform and JNK may serve as a potent and promising therapeutic approach for glioblastoma multiforme. [Read the Full Post]

Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers

1875 | May 18 2017

Morrison-Joly M et al. found that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. [Read the Full Post]

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts

0 | May 16 2017

Garreta E et al. provided a suitable platform for cardiac engineering and disease modeling in the human setting. [Read the Full Post]

Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents.

0 | May 11 2017

Tamm C et al. demonstrated that simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling.

4200 | May 07 2017

Shimada T et al suggested that neuritin and FGF cooperate in inducing mossy fiber sprouting through FGF signaling. Together, these results suggest that FGF and neuritin-mediated axonal branch induction are involved in the aggravation of epilepsy. [Read the Full Post]

Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

0 | May 06 2017

Hung MS et al. provided an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future. [Read the Full Post]

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

1609 | May 05 2017

Tang Y et al. showed that representative field potential waveforms of matured cardiac tissues with appropriate drug responses. [Read the Full Post]

MEK-ERK inhibition potentiates WAY-600-induced anti-cancer efficiency in preclinical hepatocellular carcinoma (HCC) models

1658 | May 03 2017

Wang K et al demonstrated the potent anti-HCC activity by WAY-600, either alone or with MEK-ERK inhibitors. [Read the Full Post]

Uroguanylin modulates (Na(+)+K(+))ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways.

1596 | May 01 2017

Arnaud-Batista FJ et al suggested that the molecular mechanism of action of UGN on sodium reabsorption in PT cells is more complex than previously thought. We propose that PKG-dependent activation of PKA leads to the inhibition of the mTORC2/PKB/mTORC1/S6K pathway, an important signaling pathway involved in the maintenance of the PT sodium pump expression and activity. [Read the Full Post]

Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents

1873 | Apr 30 2017

Tamm C et al. found that simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications. [Read the Full Post]

Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

1691 | Apr 29 2017

Hung MS et al. provided an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future. [Read the Full Post]

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

0 | Apr 28 2017

Han J et al suggested that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. [Read the Full Post]

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

1395 | Apr 28 2017

Tang Y et al. found that representative field potential waveforms of matured cardiac tissues with appropriate drug responses. [Read the Full Post]

Human cytomegalovirus induces an atypical activation of Akt to stimulate the survival of short-lived monocytes.

0 | Apr 24 2017

Cojohari O et al indicated that HCMV hijacks the upstream Akt signaling network to induce a nontraditional activation of Akt and subsequently a prosurvival decision at the 48-h cell fate checkpoint, a vital step for HCMV's dissemination and persistence strategy. [Read the Full Post]

Alteration of protein prenylation promotes spermatogonial differentiation and exhausts spermatogonial stem cells in newborn mice

1624 | Apr 20 2017

Diao F et al. found that the prenylation balance in germ cells is crucial for spermatogonial differentiation fate decision during the prepubertal stage. [Read the Full Post]

Activation of G protein-coupled receptor 30 by thiodiphenol promotes proliferation of estrogen receptor α-positive breast cancer cells

4403 | Apr 20 2017

Lei B et al. indicated a novel mechanism through which TDP may exert relevant estrogenic action in ERα positive cancer cells. [Read the Full Post]

Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells

0 | Apr 19 2017

Holler M et al suggested that dual targeting of mTORC1 and Akt1 inhibits repair of DNA-DSB leading to radiosensitization of solid tumor cells. [Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells.

3482 | Apr 17 2017

Choi JI et al found that addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability. [Read the Full Post]

A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer.

0 | Apr 16 2017

Ma Y et al revealed a novel EML4-ALK-HIF1α-HK2 cascade to enhance glucose metabolism in EML4-ALK-positive NSCLC. [Read the Full Post]

Ligation-free ribosome profiling of cell type-specific translation in the brain

1120 | Apr 13 2017

Hornstein N et al. applied ligation-free ribosome profiling to mouse brain tissue to identify new patterns of cell type-specific translation and test its ability to identify translational targets of mTOR signaling in the brain. [Read the Full Post]

Protein kinase B (AKT) regulates SYK activity and shuttling through 14-3-3 and importin 7

1432 | Apr 13 2017

Mohammad DK et al. suggested that AKT and 14-3-3 proteins down-regulate the activity of several BCR-associated components, including BTK, BLNK and SYK and also inhibit SYK's interaction with Importin 7. [Read the Full Post]

miR-30b inhibits autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate

0 | Apr 11 2017

Li SP et al suggested that miR-30b inhibited autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate. [Read the Full Post]

mTOR Inhibition Attenuates Dextran Sulfate Sodium-Induced Colitis by Suppressing T Cell Proliferation and Balancing TH1/TH17/Treg Profile

971 | Apr 09 2017

Hu S et al indicated that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival. [Read the Full Post]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

7234 | Apr 09 2017

Collectively, Wu C et al revealed, for the first time, a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Centrosomal Protein of 55 Regulates Glucose Metabolism, Proliferation and Apoptosis of Glioma Cells via the Akt/mTOR Signaling Pathway

1459 | Apr 08 2017

Wang G et al. found that CEP55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway, and its promotive effect on glioma tumorigenesis can be a potential target for glioma therapy in the future. [Read the Full Post]

GSK-3 directly regulates phospho-4EBP1 in renal cell carcinoma cell-line: an intrinsic subcellular mechanism for resistance to mTORC1 inhibition

963 | Apr 04 2017

Ito H et al. found that GSK-3β/4EBP1 pathway might be an important subcellular mechanism as an inherent equipment for RCC cells to acquire clinical chemoresistance to mTORC1 inhibitors. [Read the Full Post]

Distinct MicroRNA Expression Signatures of Porcine Induced Pluripotent Stem Cells under Mouse and Human ESC Culture Conditions

1547 | Apr 04 2017

Zhang W et al. found that significant differences in the miRNA signatures of hpiPSCs and mpiPSCs under different pluripotent states that were derived from different culture conditions. [Read the Full Post]

A high-throughput-compatible assay to measure the degradation of endogenous Huntingtin proteins

0 | Apr 02 2017

Peng Wu et al established the first high-throughput-compatible assay capable of measuring endogenous, tag-free HTT degradation, providing a valuable tool for HD research and drug discovery. The method could be applied to other proteins and can facilitate research on other neurodegenerative disorders and proteinopathies. [Read the Full Post]

Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

0 | Apr 01 2017

Gaudreau MC et al suggested that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. [Read the Full Post]

A Novel mTORC1-Dependent, Akt-Independent Pathway Differentiates the Gut Tropism of Regulatory and Conventional CD4 T Cells

1282 | Mar 31 2017

Chen LC et al. revealed a novel difference between ATRA signaling and chemokine receptor induction in Treg versus Tconv and provided a framework via which the migratory behavior of Treg versus Tconv might be regulated differentially for therapeutic purposes. [Read the Full Post]

DNA Topoisomerase IIα contributes to the early steps of adipogenesis in 3T3-L1 cells

0 | Mar 28 2017

Jacobsen RG et al. found that treatment of cancer with Topo II inhibitors may alter metabolic processes in the adipose tissue. [Read the Full Post]

DNA Topoisomerase IIα contributes to the early steps of adipogenesis in 3T3-L1 cells

1135 | Mar 25 2017

Jacobsen RG et al. found that treatment of cancer with Topo II inhibitors may alter metabolic processes in the adipose tissue. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

1992 | Mar 07 2017

Wu J et al. found that AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma

0 | Mar 06 2017

Agnihotri S et al. found that implicate aberrant activation of the PI3K/AKT/mTOR pathway as a molecular mechanism of pathogenesis in VS and suggest inhibition of this pathway as a potential treatment strategy. [Read the Full Post]

Dual PI3K/mTOR Inhibitors, GSK2126458 and PKI-587, Suppress Tumor Progression and Increase Radiosensitivity in Nasopharyngeal Carcinoma

0 | Mar 05 2017

Liu T et al suggested the usefulness of PI3K/mTOR dual inhibition for antitumor and radiosensitizing. The combination of IR with a dual PI3K/mTOR inhibitor, GSK2126458 or PKI-587, might be a promising therapeutic strategy for NPC. [Read the Full Post]

Suppressing Cyclooxygenase-2 prevents nonalcoholic steatohepatitis and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

1461 | Feb 27 2017

Wu J, et al.'s findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH. [Read the Full Post]

Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity

1198 | Feb 18 2017

Lee MJ et al. demonstrated that PI3Kδ regulates Dectin-2 signaling and its dendritic cell function. [Read the Full Post]

The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

1241 | Feb 16 2017

Lou HZ, et al. found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment. [Read the Full Post]

Dual targeting of mTORC1 and mTORC2 by INK-128 potently inhibits human prostate cancer cell growth in vitro and in vivo

0 | Feb 15 2017

The preclinical results of Jiang SJ, et al.'s study suggest that INK-128 could be further investigated as a promising anti-prostate cancer agent. [Read the Full Post]

The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation

5216 | Feb 12 2017

Cerniglia GJ, et al.‘s’ findings highlight an association between the PI3K/mTOR pathway and tumor cell oxygen consumption that is regulated in part by PDH phosphorylation. These results have important implications for understanding the effects of PI3K pathway activation in tumor metabolism and also in designing cancer therapy trials that use inhibitors of this pathway. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

2994 | Feb 06 2017

Kim TM, et al.'s result shows that Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

Wnt/b-Catenin-Signaling and the Formation of M€uller Glia-Derived Progenitors in the Chick Retina

1863 | Feb 04 2017

Gallina D, et al 's findings indicate that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions

1481 | Feb 02 2017

These evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine. [Read the Full Post]

Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways

1441 | Feb 02 2017

Guan JH et al. revealed the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. [Read the Full Post]

GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats

1727 | Jan 27 2017

Wang W et al. suggested that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke. [Read the Full Post]

Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina

0 | Jan 26 2017

Gallina D et al. indicated that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma

1420 | Jan 17 2017

Agnihotri S, et al.'s findings implicate aberrant activation of the PI3K/AKT/mTOR pathway as a molecular mechanism of pathogenesis in VS and suggest inhibition of this pathway as a potential treatment strategy. [Read the Full Post]

Dual PI3K/mTOR Inhibitors, GSK2126458 and PKI-587, Suppress Tumor Progression and Increase Radiosensitivity in Nasopharyngeal Carcinoma

1549 | Jan 16 2017

Liu T, et al.'s new findings suggest the usefulness of PI3K/mTOR dual inhibition for antitumor and radiosensitizing. The combination of IR with a dual PI3K/mTOR inhibitor, GSK2126458 or PKI-587, might be a promising therapeutic strategy for NPC. [Read the Full Post]

Suppressing Cyclooxygenase-2 prevents nonalcoholic steatohepatitis and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

0 | Jan 14 2017

Wu J, et al.'s findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH. [Read the Full Post]

Dual targeting of mTORC1 and mTORC2 by INK-128 potently inhibits human prostate cancer cell growth in vitro and in vivo

1285 | Jan 07 2017

Jiang SJ et al. suggested that INK-128 could be further investigated as a promising anti-prostate cancer agent. [Read the Full Post]

The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

0 | Jan 07 2017

Lou HZ, et al.‘s results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment. [Read the Full Post]

The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation

0 | Jan 04 2017

Cerniglia GJ, et al. 's results have important implications for understanding the effects of PI3K pathway activation in tumor metabolism and also in designing cancer therapy trials that use inhibitors of this pathway. [Read the Full Post]

Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina

1937 | Jan 01 2017

Gallina D et al. indicated that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

0 | Dec 31 2016

Li Y et al. suggested that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. [Read the Full Post]

Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

3233 | Dec 30 2016

Acquired resistance mechanisms of AZD9291 in patients with EGFR-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFR-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand-dependent activation. [Read the Full Post]

Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways.

1413 | Dec 29 2016

The study of Guan JH, et al. primarily revealed the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. [Read the Full Post]

Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions

1629 | Dec 28 2016

Zhang W, et al.'s evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine. [Read the Full Post]

Role of reactive oxygen species-mediated MAPK and NF-κB activation in polygonatum cyrtonema lectin-induced apoptosis and autophagy in human lung adenocarcinoma A549 cells

1652 | Dec 22 2016

Liu T, et al. found PCL may bind to the cell surface in a mannose-specific manner, and was then internalized and accumulated primarily onto the mitochondria. These findings may provide a new perspective of PCL as a potential anti-tumour drug targeting apoptosis and autophagy pathways for future cancer therapeutics. [Read the Full Post]

WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression.

2203 | Dec 21 2016

Cai T et al.'s study suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT/β-catenin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC. [Read the Full Post]

Inhibition of mTOR Signaling Pathway Delays Follicle Formation in Mice

2022 | Dec 20 2016

These results of Zhang J et al. suggested that KITL functions downstream of mTOR in somatic cells to regulate their communication with oocytes during follicle formation. J. Cell. Physiol. 232: 585-595, 2017. © 2016 Wiley Periodicals, Inc. [Read the Full Post]

Manganese-Stimulated Kisspeptin Is Mediated by the IGF-1/Akt/Mammalian Target of Rapamycin Pathway in the Prepubertal Female Rat

1478 | Dec 19 2016

Srivastava VK et al. suggested that Mn acts, at least in part, through the IGF-1/Akt/mTOR pathway to influence prepubertal kisspeptin and LHRH. [Read the Full Post]

WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

2904 | Dec 18 2016

Lu S et al. demonstrated that Akt signaling pathway mediates WISP1-induced migration and proliferation of human VSMCs, suggesting that WISP1 may act as a novel potential therapeutic target for vascular restenosis. [Read the Full Post]

Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin

2726 | Dec 15 2016

Tao L, et al. provided insight into how xanthatin and related molecules could be effectively targeted toward certain tumors. [Read the Full Post]

Exogenous HGF Prevents Cardiomyocytes from Apoptosis after Hypoxia via Up-Regulating Cell Autophagy

2344 | Dec 10 2016

Wang Y et al.'s results revealed a potential mechanism in which exogenous HGF prevented NRVMs from apoptosis after hypoxia. Upregulation of Parkin through administration of exogenous HGF may be a potential therapeutic strategy ptotecting myocytes during ischemia. [Read the Full Post]

Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression

2041 | Dec 08 2016

Jones RJ, et al. concluded LTP may reactivate EBV-positive resting memory B cells thereby enhancing EBV lytic cycle and host immune suppression. [Read the Full Post]

Upregulation of AKT3 Confers Resistance to the AKT Inhibitor MK2206 in Breast Cancer.

1965 | Dec 08 2016

Stottrup C et al. provided a rationale for developing therapeutics targeting AKT3 to circumvent acquired resistance in breast cancer. [Read the Full Post]

mTOR inhibition sensitizes human hepatocellular carcinoma cells to resminostat

1503 | Dec 07 2016

Peng X et al. suggested that mTOR could be a primary resistance factor of resminostat. Targeted inhibition of mTOR may thus significantly sensitize HCC cells to resminostat. [Read the Full Post]

Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage

2614 | Dec 06 2016

The results of Finzel A et al. revealed a new regulatory interplay in which loss of DNA-PKcs function leads to hyperactivation of ATM and amplification of the p53 response, sensitizing cells for damage-induced senescence. [Read the Full Post]

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

2269 | Dec 05 2016

Acharya S et al.’s results indicated that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. [Read the Full Post]

Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway

2920 | Dec 04 2016

Ming GF et al.'s findings suggest that the treatment of EPCs with visfatin markedly attenuates the ox-LDL-induced senescence of EPCs by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway. [Read the Full Post]

miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

2139 | Dec 04 2016

Zhang W et al.’s results demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. [Read the Full Post]

Autophagy induction contributes to GDC-0349 resistance in head and neck squamous cell carcinoma (HNSCC) cells

1422 | Dec 02 2016

The study of Zhou Y et al. provided evidences to support GDC-0349 as a promising anti-HNSCC agent. GDC-0349 sensitization may be achieved via autophagy inhibition. [Read the Full Post]

Serpine2, a potential novel target for combating melanoma metastasis

2268 | Nov 30 2016

Wu QW et al. suggested a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. [Read the Full Post]

Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo

2121 | Nov 27 2016

Wang H et al. found that erianin may be a promising agent for anticancer therapy against OS. [Read the Full Post]

Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways

3105 | Nov 24 2016

Liu SH et al. found that LIPUS stimulation might play a crucial and beneficial role in neurodegenerative diseases. [Read the Full Post]

Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression

2016 | Nov 13 2016

Li Q et al. finds that dual mTORC1/mTORC2 inhibitors such as OSI-027 are promising therapeutic agents in combination with 5-FU for the treatment of human gallbladder cancer. [Read the Full Post]

Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity

1407 | Nov 10 2016

Lee MJ et al. demonstrated that PI3Kδ regulates Dectin-2 signaling and its dendritic cell function. [Read the Full Post]

AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication

1907 | Oct 27 2016

Booth L et al. argued future patient studies with AR-12 are warranted. [Read the Full Post]

Phosphorylated heat shock protein 27 promotes lipid clearance in hepatic cells through interacting with STAT3 and activating autophagy

2390 | Oct 24 2016

Shen L et al. provided a novel mechanism by which the phosphorylated Hsp27 promotes hepatic lipid clearance and suggested a new insight for therapy of steatotic diseases such as nonalcoholic fatty liver disease (NAFLD). [Read the Full Post]

PI3K p110β isoform synergizes with JNK in the regulation of glioblastoma cell proliferation and migration through Akt and FAK inhibition

1433 | Oct 21 2016

Zhao HF et al. suggested that combined inhibition of PI3K p110β isoform and JNK may serve as a potent and promising therapeutic approach for glioblastoma multiforme. [Read the Full Post]

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts

2395 | Oct 12 2016

Garreta E et al. provided a suitable platform for cardiac engineering and disease modeling in the human setting. [Read the Full Post]

Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers

2169 | Oct 12 2016

Morrison-Joly M et al. that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. [Read the Full Post]

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

3044 | Sep 27 2016

Han J et al. suggested that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. [Read the Full Post]

Uroguanylin modulates (Na++K+)ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways

2147 | Sep 27 2016

Arnaud-Batista FJ et al. suggested that the molecular mechanism of action of UGN on sodium reabsorption in PT cells is more complex than previously thought. [Read the Full Post]

Human Cytomegalovirus Induces an Atypical Activation of Akt To Stimulate the Survival of Short-Lived Monocytes

2353 | Sep 23 2016

Cojohari O et al. demonstrated that HCMV induces the activation of Akt, an antiapoptotic protein, in a manner distinct from that of normal myeloid growth factors. [Read the Full Post]

Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells

2317 | Sep 21 2016

Holler M et al. dual targeting of mTORC1 and Akt1 inhibits repair of DNA-DSB leading to radiosensitization of solid tumor cells. [Read the Full Post]

A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer

2195 | Sep 19 2016

Ma Y et al. revealed a novel EML4-ALK-HIF1α-HK2 cascade to enhance glucose metabolism in EML4-ALK-positive NSCLC. [Read the Full Post]

miR-30b inhibits autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate

2220 | Sep 14 2016

Li SP, et al. found that miR-30b inhibited autophagy to alleviate hepatic ischemia-reperfusion injury via decreasing the Atg12-Atg5 conjugate. [Read the Full Post]

Nuclear envelope rupture and repair during cancer cell migration

1574 | Sep 12 2016

Hu S, et al. found that cell migration incurs substantial physical stress on the NE and its content and requires efficient NE and DNA damage repair for cell survival. [Read the Full Post]

A high-throughput-compatible assay to measure the degradation of endogenous Huntingtin proteins

1967 | Sep 07 2016

Peng Wu, et al. have established the first high-throughput-compatible assay capable of measuring endogenous, tag-free HTT degradation, providing a valuable tool for HD research and drug discovery. The method could be applied to other proteins and can facilitate research on other neurodegenerative disorders and proteinopathies. [Read the Full Post]

Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

2325 | Sep 06 2016

Gaudreau MC, et al. suggested that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. [Read the Full Post]

αB-crystallin induces by matrix detachment via ERK is critical in inhibition of anoikis

7878 | Mar 05 2015

Malin et al. identified an matrix detachment-induced antiapoptotic molecular chaperone, αB-crystallin, confers anoikis resistance. [Read the Full Post]

The role of DNA-dependent protein kinase in dendritic cells in house dust mite-induced asthma

4337 | Mar 03 2015

Mishra et al. demonstrated the immune role of DNA-PK in response to house dust mite (HDM) antigen in dendritic cells (DCs). [Read the Full Post]

The small GTPase Rap1b acts as a negative regulator of neutrophil recruitment to inflamed lung with acute lung injury

3485 | Feb 11 2015

Kumar et al. found small GTPase Rap1b acts as a critical suppressor of neutrophil accumulation to inflamed lungs. [Read the Full Post]

P2X7 receptor is a key upstream regulator for main signaling pathways involved in neuroblastoma progression

6478 | Feb 04 2015

Amoroso et al. demonstrated that P2X7 plays a key role in regulating the PI3K/Akt/GSK3β/MYCN and HIF1α/VEGF pathways, two main signaling pathways involved in NB progression. [Read the Full Post]

MAPK cascade promotes early axonal degeneration in response to injury

6119 | Jan 21 2015

By using traumatic injury as a model, Yang et al. demonstrated a critical role of mitogen-activated protein kinase (MAPK) cascade in early axonal degeneration in response to injury. [Read the Full Post]

The new finding of PI3K signaling regulation provides a novel therapeutic strategy for luminal breast cancer

8452 | Jan 15 2015

Costa et al. found the high efficiency of p110α inhibition by BYL719 is attenuated due to p110β accumulation. [Read the Full Post]

The mechanism of kinase independent AKT in promoting cancer development

6057 | Jan 12 2015

Vivanco et al. revealed the mechanism and emphasized a kinase-independent function of AKT in regulating cancer cell survival. [Read the Full Post]

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

12572 | Jan 07 2015

Winter et al. identified the underlying mechanism of the emerging JAK2 inhibitor therapy resistance in MPNs patients, and found the RAS and pathways mediated by AKT and ERK contribute to the resistance. [Read the Full Post]

The mechanism of GSI resistance in T cell acute lymphoblastic leukemia

5879 | Dec 30 2014

Knoechel et al. identified BRD4 is an important regulator of GSI resistance in T-ALL cells, and the combination of GSI and JQ1, the BRD4 inhibitor, is effective against T-ALL in vivo. [Read the Full Post]

Endophilin plays a central role in endocytic pathway without calthrin

3066 | Dec 24 2014

Recently, Boucrot et al. demonstrated endophillin participates in a clathrin-independent endocytic pathway, as a central component. [Read the Full Post]

CCR4 mutations act as key factors in adult T-cell leukemia/lymphoma pathogenesis

4515 | Dec 22 2014

Nakagawa et al. reported the dysregulation of CCR4 is critical in ATLL pathogenesis, and the inhibition of CCR4 signaling may have clinical value for curative treatment of ATLL. [Read the Full Post]

The Notch signaling controls maintenance of memory CD4+ T cells

10053 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

mTOR is a key regulator of rental sodium homeostasis

2457 | Nov 26 2014

Gleason et al. examined the role of mTOR in regulation of ion transport in ASDN, and demonstrated mTOR played a key role in the regulation of Na+ homeostasis, via SGK1-dependent modulation of ENaC activity. [Read the Full Post]

The combination of metformin and conventional tuberculosis drug as a new therapeutic strategy

2987 | Nov 20 2014

Singhal et al. demonstrated a diabetic drug, metformin (MET), mediates host cell responses to pathogen for promoting anti-Mtb activities. The combined regimens have shown promising positive clinical effects on tuberculosis patients.The article was published on Science Translational Medicine. [Read the Full Post]

SGK3 and INPP4B mediate PI3K signaling pathway in breast cancer

5443 | Nov 18 2014

Gasser et al. found a new PI3K signaling axis, with SGK3 and INPP4B as key factors and in the absence of Akt activity, for regulation of tumorigenesis, tumor cell proliferation and invasive migration. [Read the Full Post]

Combination of PI3K/mTOR and EGFR inhibitors suppresses KRAS-mutant colorectal cancer

7146 | Nov 14 2014

Belmont et al. demonstrated combination of PI3K/mTOR and EGFR inhibitors may become a novel therapy in patients with KRAS-mutant CRC. [Read the Full Post]

The inhibition of AKT pathway by truncated CNT-1 enhances cell apoptosis

4620 | Nov 11 2014

Nakagawa et al. demonstrated a new negative regulator of AKT signaling, tCNT-1, can promote cell apoptosis and suppress cell growth and proliferation. [Read the Full Post]

New platform of high efficiency iPSC reprogramming

8768 | Nov 05 2014

Vidal et al. found the inhibition of transforming growth factor β (TGF-β) or activation of Wnt signaling, or both, can provide a high efficient iPSC reprogramming in a cell-type-specific manner. [Read the Full Post]

Huntingtin enhances Huntington's disease via activating mTORC1 signaling pathway

3278 | Oct 31 2014

Huntington's disease causes muscle discoordination and cognitive decline. This disease is associated with huntingtin protein. William Pryor et al. found huntingtin enhances signaling of mTORC1. [Read the Full Post]

TIPE3, a new transfer protein of lipid second messengers regulates human cancer

2539 | Oct 21 2014

Svethlana et al. found one of the transfer protein, TIPE3 (TNFAIP8L3), acts as a controller of phosphoinositide second messenger that promotes cancer. IPE3 may represent a valuable target in therapeutic treatment of malignant diseases. [Read the Full Post]

Copper dependent Cancer

2269 | Apr 15 2014

Wortmannin is a PI3K with IC50 of 3 nM, first described PI3K inhibitors [Read the Full Post]

Story of Bcr Abl continues

2571 | Mar 28 2014

PP242 is a selective mTOR inhibitor with IC50 of 8 nM; targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. [Read the Full Post]

A small molecule bidentate binding dual inhibitor probe of the LRRK2 and JNK kinases

2434 | Mar 17 2014

PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM [Read the Full Post]

AZD1080 is a novel GSK3 inhibitor rescues synaptic plasticity deficits in rodent brain

3841 | Mar 06 2014

AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a Ki of 6.9 nM and 31 nM [Read the Full Post]

Perifosine is a drug candidate being developed for a variety of cancer indication

3364 | Mar 05 2014

Perifosine combining with temozolomide reduces tumor proliferation in vivo. [Read the Full Post]

Wortmannin is a specific covalent inhibitor of PI3K

2414 | Mar 03 2014

Wortmannin is a PI3K with IC50 of 3 nM, first described PI3K inhibitors, but little selectivity within the PI3K family. [Read the Full Post]

Deforolimus is a small molecule inhibitor of the mammalian target

2338 | Feb 27 2014

Ridaforolimus is a selective mTOR inhibitor with IC50 of 0.2 nM; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. [Read the Full Post]

PP242 is a new small molecule protein inhibitor

2365 | Feb 24 2014

PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ [Read the Full Post]

XL765 are frequently activated in human tumors

2315 | Feb 20 2014

SAR245409 (XL765) is a dual inhibitor of mTOR/PI3K, mostly for p110γ with IC50 of 9 nM; also inhibits DNA-PK and mTOR. [Read the Full Post]

Torin 1 is a potent and selective inhibitors of mTOR

2297 | Feb 11 2014

Torin1 inhibits phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. [Read the Full Post]

BKM120 is a potent and cell permeable inhibitor of the PI3 kinase family

2510 | Feb 07 2014

BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively. [Read the Full Post]

GDC 0068 is a highly selective small molecule inhibitor of Akt

3416 | Feb 07 2014

GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM, 620-fold selectivity over PKA. [Read the Full Post]

BKM 120 is a drug that may slow the growth of cancer cells

0 | Jan 29 2014

BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively. [Read the Full Post]

UNC0638 is an inhibitor of G9a and GLP with excellent potency and selectivity

2769 | Jan 20 2014

UNC0638 is a potent, selective and cell-penetrant chemical probe for G9a and GLP with IC50 of <15 nM and 19 nM, respectively, shows selectivity over a wide range of epigenetic and non-epigenetic targets. [Read the Full Post]

BKM 120 is a drug that may slow the growth of cancer cells

0 | Jan 17 2014

BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively. [Read the Full Post]

XL147 is an orally available inhibitor of phosphoinositide 3 kinase

2000 | Jan 08 2014

XL147 inhibits class I PI3K isoforms in an ATP-competitive manner. In a panel of HER2-overexpressing human breast cancer cell lines [Read the Full Post]

BKM 120 is a drug that may slow the growth of cancer cells

2661 | Jan 08 2014

BKM120 is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM, respectively. [Read the Full Post]

AZD1080 is a selective orally active brain permeable GSK3 inhibitor

0 | Jan 06 2014

AZD1080 reverses cognitive deficits and rescues dysfunctional synapses in mice. [Read the Full Post]

PP242 is a new small molecule protein kinase inhibitor

0 | Dec 29 2013

PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. [Read the Full Post]

Perifosine is structurally related to miltefosine

3513 | Dec 26 2013

Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. [Read the Full Post]

EPZ5676 is an Sadenosyl methionine competitive inhibitor

2301 | Dec 24 2013

EPZ-5676 reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. [Read the Full Post]

Deforolimus is a small molecule inhibitor of the mammalian target of rapamycin

2392 | Dec 19 2013

Ridaforolimus is a selective mTOR inhibitor with IC50 of 0.2 nM; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. [Read the Full Post]

Pki587 is a highly potent dual PI3K kinase inhibitor

2513 | Dec 13 2013

PKI-587 shows potent inhibitory activity against PI3K-α, PI3K-γ and mTOR with IC50 of 0.4 nM, 5.4 nM and 1.6 nM, respectively. [Read the Full Post]

Triciribine is a synthetic tricyclic nucleoside which acts as a specific inhibitor of the Akt

3641 | Dec 04 2013

Triciribine is a DNA synthesis inhibitor, also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM, respectively; does not inhibit PI3K/PDK1; 5000-fold less active in cells lacking adenosine kinase. [Read the Full Post]

Rapamycin is a bacterial macrolide with an tifungal

0 | Dec 02 2013

Rapamycin inhibits endogenous mTOR activity in HEK293 cells with IC50 of ~0.1 nM, more potently than iRap and AP21967 with IC50 of ~5 nM and ~10 nM, respectively. [Read the Full Post]

XL765 is an orally available inhibitor of PI3K

1960 | Nov 29 2013

SAR245409 (XL765) is a dual inhibitor of mTOR/PI3K, mostly for p110γ with IC50 of 9 nM . [Read the Full Post]

BYL719 is an orally bioavailable phosphatidylinositol 3 kinase inhibitor

2122 | Nov 28 2013

BYL719 is a potent and selective PI3Kα inhibitor with IC50 of 5 nM, and minimal effect on PI3Kβ/γ/δ. [Read the Full Post]

PP242 hydrate for your research needs

2365 | Nov 28 2013

PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. [Read the Full Post]

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy

2053 | Nov 26 2013

Paclitaxel is a microtubule polymer stabilizer with IC50 of 0.1 pM in human endothelial cells. [Read the Full Post]

Rapamycin is a bacterial macrolide with an tifungal

2378 | Nov 12 2013

Rapamycin (Sirolimus, AY-22989, WY-090217) is a specific mTOR inhibitor with IC50 of ~0.1 nM. [Read the Full Post]

AZD1080 is a selective orally active brain permeable GSK3 inhibitor

4417 | Nov 11 2013

AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a Ki of 6.9 nM and 31 nM, respectively, shows >14-fold selectivity against cdk2, cdk5, cdk1 and Erk2. [Read the Full Post]

IPA 3 is a selective cell permeable Pak1 inhibitor

2231 | Nov 01 2013

IPA-3 is a non ATP-competitive, allosteric inhibitor of p21-activated kinase 1 (Pak1). PIR3.5 is the control compound of IPA-3. [Read the Full Post]

Torin 1 is a potent and selective inhibitor of mTOR

2624 | Oct 31 2013

Torin1 inhibits phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. [Read the Full Post]

PP242 is a new small molecule protein kinase inhibitor

2681 | Oct 29 2013

PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. [Read the Full Post]

Temsirolimus is an intravenous drug for the treatment of renal cell carcinoma

2199 | Oct 28 2013

In the absence of FKBP12, Temsirolimus potently inhibits mTOR kinase activity with IC50 of 1.76 μM, similar to that of rapamycin with IC50 of 1.74 μM. [Read the Full Post]

CGK733 was a synthetic chemical substance which was reported in 2006

4195 | Oct 23 2013

CGK733 is able to confer robust growth to senescent cells that have ceased proliferation. [Read the Full Post]

PP242 is an inhibitor at the kinase domain of the mammalian target of rapamycin

2167 | Oct 22 2013

PP242 is able to completely inhibit the phosphorylation of Akt at S473 and T308 in fat and liver of mice. [Read the Full Post]

Triciribine was initially described as a DNA synthesis inhibitor

3522 | Aug 21 2013

Triciribine is a DNA synthesis inhibitor, also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM [Read the Full Post]

RAD001 is specific inhibitors mTOR signal

2132 | Aug 19 2013

Everolimus competes with immobilized FK 506 for binding to biotinylated FKBP12 and shows the inhibitory effect on a two-way MLR performed with spleen cells from BALB/c and CBA mice with IC50 of 0.12-1.8 nM. [Read the Full Post]

Tideglusib might be useful for slowing atrophy rates

3879 | Aug 15 2013

Tideglusib (NP031112, NP-12) is an irreversible, non ATP-competitive GSK-3β inhibitor with IC50 of 60 nM; fails to inhibit kinases with a Cys homologous to Cys-199 located in the active site. Phase 1/2. [Read the Full Post]

TWS119 is thought to bind GSK with high affinity

4350 | Jul 11 2013

Treatment of a monolayer of P19 cells with 1 μM TWS119 causes 30–40% cells to differentiate specifically into neuronal lineages based on counting of TuJ1 positive cells with correct neuronal morphology (up to 60% neuronal differentiation occurred through the standard EB formation protocol with concomitant TWS119 treatment). [Read the Full Post]

Perifosine is a drug candidate being developed for a variety of cancer indications

3429 | Jul 09 2013

Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. [Read the Full Post]

RAD001 treatment will shrink or slow the growth of the vestibular

2192 | Jul 01 2013

Everolimus exhibits the immunosuppressive activity which is comparable to that of rapamycin. Everolimus competes with immobilized FK 506 for binding to biotinylated FKBP12 and shows the inhibitory effect on a two-way MLR performed with spleen cells from BALB/c and CBA mice with IC50 of 0.12-1.8 nM. [Read the Full Post]

GDC 0941 is a potent inhibitor the PI3 kinase family

2705 | Jun 13 2013

GDC-0941 is equipotent against PI3Kα and PI3K as well as PI3Kα mutants E545-K and H1047-R, displaying modest levels of selectivity against PI3Kβ (10-fold) and PI3Kγ (25-fold) [Read the Full Post]

Tideglusib may be useful for slowing atrophy rates

4264 | Jun 05 2013

Tideglusib (50 mg/kg) injected into the adult male Wistar rats hippocampus dramatically reduces kainic acid-induced inflammation and has a neuroprotective effect in the damaged areas of the hippocampus. [Read the Full Post]

INK 128 is a potent and selective mTOR inhibitor with IC50 of 1 nM

2801 | May 28 2013

INK 128 exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases. [Read the Full Post]

Ridaforolimus is a smallmolecule inhibitor of mTOR

2247 | Jan 30 2013

Upon activation of PI3-K, the serine?Cthreonine kinase phosphoinositide-dependent kinase 1 is translocated to the membrane by binding of its PH domain to the second messenger PIP3. PDK1 can activate a variety of kinases from the AGC family including PKB, p70 ribosomal S6 kinase and several Ridaforolimus isoforms of protein kinase C . [Read the Full Post]

PI3K AKT Signaling Pathways is an intracellular signalling pathway important in apoptosis

1773 | Jan 08 2013

Classical non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, PI3K AKT Signaling Pathways naproxen, and ibuprofen are known to reduce inflammation by blocking the formation of prostaglandins (PG) and thromboxanes through inhibition of cyclooxygenase (COX)-1 and COX-2 [1]. [Read the Full Post]

Cells subjected to ATM inhibitor Ku55933

3948 | Dec 18 2012

Antineoplastic drugs play an important role in cancer therapy. A growing number of patients and new fields of application have resulted in an increasing use of these agents. Most ATM inhibition antineoplastic drugs have carcinogenic, mutagenic and teratogenic properties. [Read the Full Post]

DNA PK Inhibitors is a trimeric nuclear serine kinase composed of a large catalytic subunit

3967 | Dec 11 2012

Over the past year, multiple new systemic therapy agents have become available to treat men with metastatic castration resistant prostate cancer mCRPC that provide modest but much needed benefits Table . [Read the Full Post]

PI-103, as a potent class I PI3K inhibitor

3801 | Oct 21 2012

CHARACTERIZATION of PI-103 So far, there are a lot of PI3K isozyme-selective allosteric inhibitors that have been reported. For example, PIK-75 is a p110alpha-specific inhibitor, TGX-221 is a p110beta-specific inhibitor and IC87114 is a p110delta-specific inhibitor. These PI3K inhibitors are promising agents in the treatment of cancer and other diseases, and PI-103 is one of them. PI-103 is a potent, cell-permeable, ATP-competitive class I PI3K inhibitor. The structure analysis indicates that PI-103 is a pyridinylfuranopyrimidine molecule and ATP-competitive PI3K inhibitor. PI-103 has the solubility around 24 mg/mL in both dimethyl sulfoxide (DMSO), however it is scarcely soluble in ethanol and water with solubility of less than 1 mg/mL. And the approximate price of PI-103 is $151 per 10 mg and $466 per 50 mg in selleckchem.com, and PI-103 price may vary according to the proportion purity of the preparation and/or from one PI-103 supplier to different ones. [Read the Full Post]

GDC-0941 as a potent PI3K inhibitor

3528 | Oct 19 2012

CHARACTERIZATION OF GDC-0941 PI3 kinases are identified as the lipid kinases, which involve in the regulation of breast tumor cell growth, migration, and survival. So far, there are a lot of PI3K isozyme-selective inhibitors that have been reported as the potential therapy drugs against tumors or other diseases, and GDC-0941 is one member of them. GDC-0941 is an orally bioavailable class I selective PI3K inhibitor, and produces the antitumor activity in human cancer cell lines in vitro and in vivo cancer models. GDC-0941 is a thieno[3,2-d]pyrimidine derivatives, and interacts with residues outside the active site of p110. [1] GDC-0941 has the solubility around 103 mg/mL in dimethyl sulfoxide (DMSO) , however it is scarcely soluble in both water and ethanol with solubility of less than 1 mg/mL. And the approximate price of GDC-0941 is $214 per 10 mg and $466 per 50 mg in selleckchem.com, and GDC-0941 price may vary according to the proportion purity of the preparation and/or from one GDC-0941 supplier to different ones. [Read the Full Post]

PI-103, a multi-kinase inhibitor

7033 | Oct 17 2012

PI-103 According to the critical roles of PI3K for cell growth and survival, a series of isoform-selective inhibitors of the PI3 kinase family, such as PI-103, PIK-90, and TGX-468 are synthesized and identified to block phosphorylation of Akt, the downstream effector of PI3 kinase in cancer cell lines. PI103 is a promising tricyclic pyridofuropyrimidine lead and chemical tool compound, and a potent inhibitor with low IC50 values against recombinant PI3K isoforms including p110alpha, p110beta, p110delta,, and p110gamma. Besides, PI-103 also produces effective inhibitory activity against mTORC1 and DNA-PK in the low concentration. In preclinical studies, PI-103 potently inhibits proliferation and invasion of human cancer cells, and shows antiangiogenic potential. Moreover, PI-103 also enhances the induction of mitochondrial apoptosis by enhances downstream p53 signaling . [Read the Full Post]

MK-2206, a potent Akt inhibitor

6694 | Oct 16 2012

Characterization of MK-2206 Akt is identified as a serine-threonine kinase on the basis of its homology to protein kinase A (PKA), protein kinase C (PKC) and the retroviral oncogene, viral Akt. The known three human AKT isozymes (Akt1, Akt2 and Akt3) are highly homologous multi-domain proteins with both overlapping and distinct cellular functions. So far, there are a lot of AKT isozyme-selective allosteric inhibitors that have been reported, and MK-2206 is one member of them. MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms, which binds to a site outside the PH domain and binds very weakly to the PH domain of Akt. MK-2206 has the solubility around 96 mg/mL in both dimethyl sulfoxide (DMSO) and water, however it is scarcely soluble in ethanol with solubility of 2 mg/mL. And the approximate price of MK-2206 is $214 per 10 mg and $718 per 50 mg in selleckchem.com, and MK-2206 price may vary according to the proportion purity of the preparation and/or from one MK-2206 supplier to different ones. [Read the Full Post]

Perifosine as a potent Akt inhibitor

4965 | Oct 15 2012

FEATURES OF PERIFOSINE Perifosine, also known as KRX-0401, is a synthetic novel alkylphospholipid (ALP) and a potent antitumor agents which inhibits PH domain mediated AKT membrane recruitment and activation. Perifosine structure has been elucidated through X-ray crystallography and it shows the similar structure with phospholipids that are the main constituents of cellular membranes. Perifosine is soluble in water and ethanol with solubility of 14 mg/mL and 92 mg/mL, respectively. But Perifosine solubility in DMSO is poor. Commercially researchers can obtain Perifosine with the price of about $210/mg from suppliers selleck chemicals. Perifosine stability keeps good for at least 2 years for the dry solid when stored at -20°C and for 6 months at -80°C in DMSO. [Read the Full Post]

GDC-0941, A NOVEL PI3K INHIBITOR

9979 | Oct 12 2012

GDC-0941 As is known, there have been several identified PI3 kinases, which are divided into classes IA, 1B, II, and III according to the differences of sequence homology and substrate preference. Besides, the PI3K superfamily also includes the Class IV PIK related enzyme family of protein kinases including mTOR, ATM, ATR, and DNA-PK. Of which, Class IA PI3K is a heterodimer composed of a p110 catalytic subunit and a p85 regulatory subunit, and there are three variants of the p110 catalytic subunit designated p110α, β, or δ catalytic subunit. PI3 Kinase is an oncogene that is commonly mutated in cancer. Hence inhibition of PI3K, and in particular p110α, is a promising target for cancer treatment. [Read the Full Post]

MK-2206, as a pan Akt inhibitor

7920 | Oct 09 2012

MK-2206 AKT/Protein Kinase B is a serine/threonine-specific protein kinase that constitutes an important pathway that regulates the signaling of multiple essential biological processes such as glucose metabolism, apoptosis, cell proliferation, and cell migration. AKT can be recruited to the membrane and activated with increases in PIP3 induced by PI3K. Since activating mutations of PI3K occur in human tumors, the AKT pathway is a promising potential target for cancer chemotherapy. MK-2206, is identified as an orally bioavailable allosteric inhibitor of Akt with potential antineoplastic activity. MK-2206 has shown cytotoxic activity in vitro cell line, such as T-cell acute lymphoblastic leukemia (T-ALL), and the efficacy of MK-2206 also has been proven in preclinical models of human cancers. [Read the Full Post]

Everolimus, as a derivative of rapamycin

4262 | Oct 08 2012

CHARACTERIZATION OF EVEROLIMUS The PI3K/Akt/mTOR pathway plays a important role in various cellular processes including cell growth, proliferation, survival, and metabolism. is found to be constitutively activated in multiple tumor cells, providing potential targets for anticancer therapy. Everolimus, also known as RAD001, is a potent and highly specific mTOR inhibitor. Everolimus, together with Temsirolimus, are both important derivatives of Rapamycin. Everolimus structure reveals that it is an immunosuppressive macrolide [1] bearing a stable 2-hydroxyethyl chain substitution at position 40 on the rapamycin structure. Everolimus has the solubility around 192 mg/mL in both dimethyl sulfoxide (DMSO) and ethanol, however it is scarcely soluble in water. And the approximate price of Everolimus is $670 per 100 mg in selleckchem.com and Everolimus price may vary according to the proportion purity of the preparation and/or from one Everolimus supplier to different ones. [Read the Full Post]

Everolimus, as a mTOR inhibitor

7264 | Sep 26 2012

EVEROLIMUS Everolimus, also known as RAD001 or SDZ RAD, is a orally active rapamycin analog with potent immunosuppressive activity. Similar with rapamycin, Everolimus is also identified as a potent inhibitor against mammalian target of rapamycin (mTOR). The preclinical trials in vitro and in vivo indicate that Everolimus as an immunosuppressant efficiently inhibits antigen-driven proliferation of human T-cell clones and prevents graft rejection in rat models of allotransplantation. In addition, Everolimus as an mTOR inhibitor also shows potential anti-tumor activity for treatment of multiple cancers. [Read the Full Post]

BEZ235 as a dual PI3K/mTOR inhibitor

2938 | Sep 23 2012

Characterization of BEZ235 The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin inhibitor (mTOR) pathway involves in various cellular processes including cell growth, proliferation, survival, and metabolism. is often constitutively activated in human tumor cells, providing unique opportunities for anticancer therapeutic intervention. BEZ235, also known as NVP-BEZ235, is a potent and highly specific oral dual mTOR/PI3K inhibitor. BEZ235 structure reveals that it is an imidazoquinoline derivative, and is shown to be toxic to Waldenström's macroglobulinemia cells. BEZ235 has the solubility around 7 mg/mL in dimethyl sulfoxide (DMSO) however it is scarcely soluble in water and ethanol. And the approximate price of BEZ235 is $170 per 100 mg and BEZ235 price may vary according to the proportion purity of the preparation and/or from one BEZ235 supplier to different ones . [Read the Full Post]

PERIFOSINE, A NOVEL AKT INHIBITOR

3743 | Sep 20 2012

PERIFOSINE Perifosine, also called D-21266 or KRX-0401, is identified as a heterocyclic alkylphospholipid and a drug candidate being developed for a variety of cancers. Perifosine is an orally active ark inhibitor which is completely bioavailable with antitumor capacities. Perifosine has displayed significant anti-proliferative and pro-apoptosis activity in vitro in vitro and in vivo, and now is currently being tested in different clinical trials. [Read the Full Post]

INHIBITION OF mTOR FOR CANCER THERAPEUTICS

2899 | Sep 17 2012

SIGNALLING BY mTOR: A serine/threonine kinase protein named as mTOR stands for the “mammalian target of Rapamycin”. It is also known as FRAP1 that is a FK506-binding protein 12 - rapamycin associated protein-1. FRAP1 is the gene that is responsible of encoding this protein. mTOR protein is involved in many processes in the cell like cell survival, cell growth and proliferation, migration of proteins and the transcriptional regulation of cell. The mTOR regulatory proteins regulate these processes in response to the nutrient and energy status of the cell. mTOR can be an attractive target for the cancer therapy due to its active role in the different cellular processes like growth, proliferation and survival of the cell. Hence some specific mtorc2 inhibitors are synthesized that have the capability of controlling the cancer development and progression by inhibiting the functions performed by mTOR proteins. So by inhibiting the mTOR signaling pathway we can control the growth of tumor and check the tumorigenesis. [Read the Full Post]

BEZ235-dual PI3K/mTOR inhibitor

8027 | Sep 15 2012

BEZ235 (NVP-BEZ235) BEZ235 is a novel orally-bioavailable PI3-kinase inhibitor, and shows strong antiproliferative and apoptotic activity in breast cancer, prostate cancer, and myeloma cell lines. In vivo study indicates that BEZ235 produces antitumor activity in xenograft models harboring PI3K pathway alterations. In preclinical toxicology studies, BEZ235 treatment is well tolerated. [Read the Full Post]

EVEROLIMUS- mTOR PATHWAY INHIBITOR

3727 | Sep 04 2012

EVEROLIMUS Regulatory activities of the cell that are associated with its multiplication, movement, transcription and additionally in translation of the genes is controlled by mTOR pathway that is among the necessary numerous cell cycle regulators. FRAP1 gene is translated to provide mTOR that phosphorylates serine/threonine residue of proteins. Cancer typically arises from the down-regulation of this mTOR cascade. Therefore for targeted cancer therapy proteins like are also taken into consideration. Different types of inhibitors are being searched and Everolimus mTOR inhibitor is amongst the very promising inhibitors. Novartis that is pharmaceutical company created it and sell it with as Afinitor Everolimus that is its trade name. Since structural studies revealed that Everolimus may be a derivative of 40-O-(2-hydroxyethyl), the pharmacokinetic properties are appeared to be improved owing to the availability of oxygen atom the 40 position. Against mTOR Everolimus IC50 is approximately 1nM. Around 100mg/ml of DMSO is appropriate for Everolimus solubility. It is water and ethanol soluble. The mode of administration of Everolimus is via oral route and it is present in 5mg of packaging and approximately $60 is Everolimus price. Dry-ice is used for its distribution. [Read the Full Post]

INHIBITING mTOR IN CANCER THERAPY

2678 | Aug 14 2012

SIGNALLING VIA mTOR: mTOR is serine/threonine kinase protein and stands for “mammalian target of Rapamycin”. It also known as FRAP1 i.e., FK506-binding protein 12 - rapamycin associated protein-1. It as encoded by a gene known as FRAP1.mTOR is known to be involved in controlling various cellular processes for example; cell growth, survival, proliferation, transcriptional regulation and migration of proteins. mTOR regulatory proteins function in these processes by responding to the energy and nutrient status of the cell. As mTOR is involved in lots of cellular processes regarding its growth proliferation and survival, it can provide a target in cancer therapy; therefore, mTORc1 inhibitors have been designed that can control the cancer progression and development by inhibiting the functions mTOR performs. Inhibiting mTOR signaling pathway thus controls the tumor growth and limits tumorigenesis. [Read the Full Post]

INHIBITON OF AKT FOR THE TREATMENT OF CANCER

4007 | Aug 10 2012

CELL PROLIFERATION AND AKT PATHWAY Signal transduction pathways involve various types of kinase enzymes. AKT kinase is such an enzyme that is responsible of phosphorylating the proteins on their specifically serine/threonine sites specifically. It is also named as PKB which means Protein kinase B. It is involved in different kinds of cellular processes like apoptosis, transcription, translation, metabolism and the most important of above all is the cell proliferation and cell migration. Many cancerous cells have been found to exhibit AKT dysfunction therefore it is thought to have an important role in the regulation of cell cycle. AKT pathway gets active by stimulation from PI3K and it also activates by itself mTOR protein to initiate the further process. When PI3K gets hyperactivated, there is an increase in rate of cell division process etc. hence caused tumorigenesis. As compared to any other pathway of signal transduction, this AKT pathway exists more frequently in the cancer cells due to event of amplification, mutation and translocation in its kinase proteins. To fight against various types of cancers and tumors the strategy applied is to target any one of these kinase proteins of this pathway and the AKT inhibitors were found quite good to be used for the treatment of cancer. [Read the Full Post]

INHIBITON OF AKT TO FIGHT CANCER

4027 | Aug 06 2012

AKT PATHWAY AND CELL PROLIFERATION Different types of kinases are involved in the signal transduction pathways. AKT kinase is one such kinase that specifically phosphorylates proteins at their serine/threonine amino acids site. It is also called as PKB i.e., Protein kinase B and is involved multiple types of cellular processes e.g., glucose metabolism, transcription, translation, apoptosis and important of all cell proliferation and its migration. Many of the cancer cells have been found to have AKT dysfunction in them therefore it is considered to have a very important role in cell cycle regulation. AKT gets activated by PI3K and activates itself mTOR protein and further process in the cell gets initiated. Hyperactivation of PI3K increases the rate of cellular process of division etc. and hence takes part in tumorigenesis. This pathway is more frequently found in cancer than any other signal transduction pathway due to the occurrence of mutation, translocation and amplification in its protein kinases. Targeting one of the kinases of this pathway is the strategy to fight against many types of cancers and PKB inhibitors have been found to be quite feasible to be used against cancer. [Read the Full Post]

mTOR INHIBITORS AND CANCER THERAPY

3328 | Jul 31 2012

mTOR SIGNALING PATHWAY: FRAP1 or FK506-binding protein 12 - rapamycin associated protein-1 is another name of mTOR (mammalian target of rapamycin) which is a serine/threonine protein kinase and encoded by FRAP1gene in human genome. Many of the cellular processes are reported to be controlled by mTOR which is in response to nutrient and energy status, these processes includes cell proliferation, cell growth, transcriptional regulation migration of proteins and cell survival. Therefore a straight forward approach is to design mTOR inhibitors that would control the process of mTOR by inhibiting its actions in the cancer cells where normal processes are aberrant. mTOR signaling pathway can be checked by these inhibitors leading to control of tumor and cell growth or limiting tumorigenesis. [Read the Full Post]

AKT INHIBITORS AS ANTI TUMOR AGENTS

4367 | Jul 24 2012

AKT PATHWAY AND CANCERS: AKT is a kinase specific for threonine/serine amino acids which is also known as Protein kinase kinase B (PKB). This kinase is involved in various cellular pathways such as glucose metabolism, apoptosis, transcription and the most important functions are cell migration and proliferation. In cancer cells many of the crucial functions are controlled by AKT which depicts its importance. AKT is downstream to PI3K and mostly it is hyper activated during formations of cancers therefore taking a part in tumorigenesis through a hyperactive PI3K/AKT/mTOR pathway. As mutations, translocations and amplifications in PI3K/AKT/mTOR pathway result into hyperactivation of this pathway are more frequent than other signaling pathways. AKT inhibitors are one of the most feasible approaches to fight against cancer. [Read the Full Post]

RAPAMYCIN-A BROAD SPECTRUM DRUG

3248 | Jul 22 2012

RAPAMYCIN- INHIBITS mTOR In all around the world the treatment of cancer is a hot topic of research and as a result of extensive work in this field many of the novel therapeutic agents are undergoing clinical trials in order to sort out drugs with least side effects. In research and development efficacy is not the only thing which is under considerations but also the specificity. In cancer treatment the drugs are mostly designed as regulatory or inhibitory agents for cell cycle proteins. Rapamycin 53123-88-9 is one such inhibitor which targets mTOR protein kinase enzyme. Checking the functions of mTOR proteins cellular growth and proliferation can be controlled by affecting transcription and translation of specific genes. Rapamycin mTOR inhibitor is being used since decades for the treatment of cancer. One of the effective results has been reported for cancer cure and some other disorders are also noted to be treated by this drug. Four decades back this inhibitor was discovered as an anti-fungal drug. Rapamycin is also used for transplantation cases where it acts as an immunosuppressing compound as it also inhibits cell cycle process. One of the major usages of this compound is its application for HIV treatment. [Read the Full Post]

TEMSIROLIMUS

3419 | Jul 16 2012

TEMSIROLIMUS: INHIBITOR OF mTO RPATHWAY Protein kinase mTOR are the enzymes that come under the category of phosphatidylinositol 3-kinase or PI3-K that control the cell migration, cell multiplication, cell transcriptional and translational actions and cell survival. The fact that these inhibitors are involved in the above described processes, these enzymes have come into lime light for cancer therapy. In the recent years Temsirolimus mTOR inhibitor has got more popularity as compared to Rapamycin which was employed in the late years. For the cure of RCC or renal cell carcinoma Temsirolimus Torisel is among the rare inhibitors which is waiting for its approval by FDA. Temsirolimus 162635-04-3 is developed by a pharmaceutical company called Wyeth and it is administered to the patientsintravenously. [Read the Full Post]

TEMSIROLIMUS

3096 | Jul 10 2012

TEMSIROLIMUS: AN INHIBITOR OF mTOR Protein kinase mTOR are the enzymes that come under the category of phosphatidylinositol 3-kinase or PI3-K that control the cell migration, cell multiplication, cell transcriptional and translational actions and cell survival. The fact that these inhibitors are involved in the above described processes, these enzymes have come into lime light for cancer therapy. In the recent years Temsirolimus mTOR inhibitor has got more popularity as compared to Rapamycin which was used in the late years. [Read the Full Post]

TEMSIROLIMUS

3699 | Jul 03 2012

TEMSIROLIMUS: mTOR INHIBITOR mTOR belongs to phosphatidylinositol 3-kinase family which are the protein kinases that regulate cell survival, growth, proliferation, transcriptional activities, cell migration and protein synthesis. Due to the involvement of these in above mentioned processes they have gained importance from therapy point of view in cancer treatment. In comparison to Rapamycin Temsirolimus mTOR inhibitor gained importance for the past few years. [Read the Full Post]

TEMSIROLIMUS

2817 | Jul 02 2012

TEMSIROLIMUS ASmTOR INHIBITOR mTOR belongs to phosphatidylinositol 3-kinasefamily which are the protein kinases that regulate cell survival, growth, proliferation, transcriptional activities, cell migration and protein synthesis. Due to the involvement of these in above mentioned processes they have gained importance from therapy point of view in cancer treatment. In cosmparison to RapamycinTemsirolimus mTOR inhibitor gained importance for the past few years. [Read the Full Post]

EVEROLIMUS-AN INHIBITOR OF mTOR PATHWAY

3063 | Jun 29 2012

EVEROLIMUS: INTRODUCTION mTOR pathway is among the different vital regulators of cell cycle which are involved in its regulatory activities likecell proliferation, growth, migration and activities related to transcription and translation. mTOR is the translational product of FRAP1 gene which phosphorylates threonine/serine residues in protein. Defected or dysregulated mTOR pathway is a common reason of developing cancerous cells. Therefore, these proteins are also targeted while looking for an effective anti-cancer therapy. Everolimus mTOR inhibitor is among the efficientinhibitors that have been searched so far. Afinitor Everolimus is the brand name of inhibitor and developed by Novartis. Everolimus structure contains 40-O-(2-hydroxyethyl) derivative and properties related to ispharmacokinetics are found to be improved by the presence of oxygen at position 40. Everolimus IC50 for mTOR is around 1nM. Everolimus solubility is 100mg per ml of DMSO while it is also soluble in ethanol and water. It is administered orally and Everolimus price $60 in packaging of 5mg.It is distributed in dry ice. [Read the Full Post]

TEMSIROLIMUS

3042 | Jun 11 2012

TEMSIROLIMUS: mTOR INHIBITOR Protein kinase mTOR are the enzymes that come under the category of phosphatidylinositol 3-kinase or PI3-K that control the cell migration, cell multiplication, cell transcriptional and translational actions and cell survival. The fact that these inhibitors are involved in the above described processes, these enzymes have come into lime light for cancer therapy. In the recent years Temsirolimus mTOR inhibitor has got more popularity as compared to Rapamycin which was used in the late years. [Read the Full Post]

EVEROLIMUS-AN mTOR INHIBITOR

3131 | Jun 05 2012

mTOR PATHWAY AND EVEROLIMUS Regulatory activities of the cell that are related to its multiplication, movement, transcription and as well as translation of the genes is controlled by mTOR pathway which is one of the important various cell cycle regulators. FRAP1 gene is translated to produce mTOR which phosphorylates serine/threonine residue of proteins. Cancer usually arises from the down-regulation of this mTOR cascade. So for targeted cancer therapy proteins like it are also taken under consideration [1].Different types of inhibitors are being searched and Everolimus mTOR inhibitoris one of the very promising inhibitors [2]. Novartis which is pharmaceutical company produced it and sell it with as Afinitor Everolimus which is its trade name. Since structural studies revealed that Everolimus is a derivative of 40-O-(2-hydroxyethyl), the pharmacokinetic properties are seemed to be improved due to the availability of oxygen atom the 40 position. Against mTOR Everolimus IC50 is approximately 1nM.Around 100mg/ml of DMSO is suitable for Everolimus solubility. It is water and ethanol soluble. The mode of administration of Everolimus is through oral route and it is present in 5mg of packaging and approximately $60 is Everolimus price. Dry-ice is used for its distribution. [Read the Full Post]

RAD001 – THE mTOR INHIBITOR

3104 | May 29 2012

RAD001: The mTOR protein which is also known as Rapamycin’s mammalian target protein is famous threonine or serine protein kinase enzyme. This kinase plays several significant roles including cellular survival, cell division, migration of cells and also in regulating a good numbers of transcriptional events linked to a huge number of signaling cascades such as aging. There are several research reports mentioning the involvement of abrupt mTOR pathway in cancer and tumorigenesis, due to this fact this pathway has become a target for the cure of large number of cancers [1]. Different mTOR inhibitors has been generated and tested, amongst these inhibitors RAD001 mTOR inhibitor is orally bio-available chemical [2]. This is developed by Novartis and is recognized under the name, Everolimus. RAD001 can be purchased easily from RAD001 supplier. According to the RAD001 structure it contains 40-O-(2-hydroxyethyl) but it is a derivative of this compound in order to enhance its pharmacokinetics. For appropriate inhibition of mTOR pathway RAD IC50 is about 1nM. The RAD001 solubility can be gained in ethnol and water as well where as a 100mg/ml solution can be gained in DMSO. If someone wants to purchase RAD001 on can pay RAD001 price of 50$ and get a vial of 5mg. One main property of this compound is its action on mTOR1 pathway rather than mTOR2 pathway as it does not affect. [Read the Full Post]

TEMSIROLIMUS

2591 | May 27 2012

TEMSIROLIMUS: mTOR INHIBITOR mTOR protein kinase enzymes are the proteins that belongs to PI3-K (phosphatidylinositol 3-kinase) which is associated with the family of kinase proteins and are responsible for regulation of cell survival, growth, proliferation, transcriptional activities, cell migration and protein synthesis. Just because of the effect of these inhibitors on the above mentioned phenomenon, the targeting of these enzymes to treat various types of cancers is now an attractive approach. In past Rapamycin was known to be the most valuable inhibiting drug that belongs to the class of mTOR inhibitors but now days another member of this family named Temsirolimus mTOR inhibitor is more famous than that one. [Read the Full Post]

EVEROLIMUS-AN mTOR INHIBITOR

2893 | May 25 2012

mTOR PATHWAY AND EVEROLIMUS Among different cell cycle regulatory pathways, mTOR pathway is an important one as it is involved in a lot of regulatory activities related to cell proliferation, growth, migration and activities related to transcription and translation. mTOR is actually serine/threonine protein kinase that is a product of FRAP1 gene. Defected or dysregulated mTOR pathway is a common reason of developing cancerous cells. Therefore, these proteins are also targeted while looking for an effective anti-cancer therapy [1]. For this purpose many inhibitors against these proteins are being researched. One of these efficiently acting inhibitors is the Everolimus mTOR inhibitor [2]. It is marketed by pharmaceutical company Novartis and is available under the trade name of Afinitor Everolimus. Everolimus structure is a 40-O-(2-hydroxyethyl) derivative where oxygen at position 40 is known to improve its pharmacokinetic properties. Everolimus IC50 against mTOR is around 1 nM. Everolimus solubility can be achieved upto 100 mg/ml in DMSO. It is also soluble in ethanol and water. Everolimus is an orally administered drug and is available in the form of a vial of 5 mg with an Everolimus price of around $60. It is distributed in dry ice. [Read the Full Post]

TEMSIROLIMUS

2449 | May 09 2012

TEMSIROLIMUS AND mTOR INHIBITORS:  mTOR protein kinases belonging to phosphatidylinositol 3-kinase (PI3-K) which is related to the family of kinase proteins are responsible to regulate cell growth, survival, proliferation, protein synthesis, cell’s transcriptional activities and cell migration. Because of their influence on all of the above mentioned processes, targeting many of these enzymes for the treatment of various diseases is now a very valuable approach. Previously Rapamycin was found to be the most famous inhibitor belonging to category mTOR but these days another member of same family named as Temsirolimus mTOR inhibitor is also getting popularity. [Read the Full Post]

EVEROLIMUS: TEARING mTOR PATHWAYS

2387 | May 03 2012

EVEROLIMUS: Mammalian target of Rapamycin abbreviated as mTOR is a serine/threonine protein kinase enzyme encoded by the FRAP1 gene involving in different transcriptional events, regulation of aging, and in cell invasion, survival and proliferation pathways. In cancers, the Dysregulation of mTOR cascade is a very common event that makes it a promising and attractive target for the anti-tumor therapies [1]. Among those many inhibiting drugs tried for the sake of treating cancers, Everolimus mTOR inhibitor is one of the best [2]. The trade name of this inhibiting drug is Afinitor Everolimus and is marketed by the company Novartis. It is an orally administered medicine and is a derivative of 40-O-(2-hydroxyethyl). Everolimus IC50 is found to be around 1 nM. In Everolimus structure a 2-hydroxyethyl chain at 40th Oxygen molecule improves its pharmacokinetic properties. Everolimus sulobility is best in DMSO (100 mg/ml) and ethanol as it is an oral drug but is also achievable in water. Everolimus price is about $60 for 5 mg vial and the Everolimus suppliers distribute it in the dry ice. [Read the Full Post]

RAPAMYCIN-A MULTI PURPOSE DRUG

3587 | Apr 27 2012

RAPAMYCIN- AN mTOR INHIBITOR Cancer and its treatment has been an active area of research and a lot of new drugs are in clinical trials in order to find an efficacious drug against cancer having least side effects. In addition to efficacy, specificity is also an issue that is being considered in research. Most of the drugs being researched are cell cycle regulatory protein inhibitors. Rapamycin is also one of them which are an mTOR protein kinase inhibitor. Inhibiting mTOR proteins may modify cell growth, proliferation, migration and activities related to transcription and translation thus preventing cancer cell proliferation. Rapamycin mTOR inhibitor had been used since decades for treatment against cancer. Although it’s most efficient use has been seen for cancer, it is used for the treatment of other diseases too. It has been four decades since this inhibitor has been discovered as anti-fungal agent. [Read the Full Post]

TEMSIROLIMUS- AN mTOR INHIBITOR

2609 | Apr 18 2012

TEMSIROLIMUS Different types of protein kinases are there that function in the cell signaling process for the activation or inhibition of cellular processes like gene expression for division, growth, differentiation etc. mTOR protein kinases are one of such cell cycle regulatory proteins. They belong to PI3-K (phosphatidylinositol 3-kinase) related kinase family of proteins. mTOR proteins are involved in the regulation of proliferation of cells, growth, cell survival and migration, synthesis of proteins and activities related to transcription in the cell. As they influence a lot of cell cycle regulating pathways, any disturbance in these or the proteins which they influence, may cause cancer in the tissue. Therefore these mTOR proteins are the best targets for anti-cancer drugs. Rapamycin is one of these mTOR inhibitors which are well known. Temsirolimus mTOR inhibitor, another important inhibitor is being researched nowadays. [Read the Full Post]

RAPAMYCIN

2083 | Apr 01 2012

RAPAMYCIN AND mTOR INHIBITORS: In the era of cancer therapy, more and more efficient and safer drugs are needed than the traditional chemotherapeutic agents. New drugs are needed to be designed in such a way that they spare normal cells but targeting the abnormal cancerous cells. Among many abnormal pathways one is mTOR pathway which is mostly present in cancer cells, thereby use of mTOR inhibitors is one the potential approach for cancer treatment. One of such drug is RapamycinmTOR inhibitor that is being used for decades as a therapeutic. Almost 40 years back Rapamycin was discovered as an antifungal antibiotic and later on it started to be used as a strong immunosuppressant for transplant studies and in these studies it was considered to be an inhibitor of cell cycle. More recently it was used for the treatment of HIV as immunosuppressant because of its popularity but the most applied uses are in cancer treatment. [Read the Full Post]

SUCCESS OF mTOR INHIBITOR IN CLINICS

2515 | Mar 19 2012

Introduction: The mTOR Pathway and its clinical importance In 1994 a protein was discovered that was determined to be a target for the small molecule inhibitor Rapamycin, it was named mTOR. The acronym mTOR stands for the “mammalian Target for Rapamycin” and this protein was demonstrated to be essential for embryonic development, mutated null murine models did not survive in utero. Subsequent investigation revealed that the mTOR protein is like the “Grand central station” of multiple regulatory pathways dealing mostly with gene transcription and cell growth. The unique aspect of the mTOR protein is that despite being more related to lipid kinases it also has functions similar to those of the serine/threonine kinase family phosphoinositide 3-kinase related kinases (PIKK). [Read the Full Post]

KU-0063794 - THE NEW mTOR INHIBITOR

2387 | Mar 19 2012

Introduction: The mTOR pathway Since many of the protein kinases are structurally similar their effects in the signaling sequence sometimes overlap. One of the central points of a several different pathways is the mTOR protein. Located mostly in the cytosole this protein can receive signals directly from the extracellular system as well as regulation by cell membrane induced signals. Discovered in relation to the then unknown target for a molecule called rapamycin this protein was name mTOR (“mammalian Target For Rapamycin”), not an original name but serves the purpose. Downstream signaling of the mTOR protein can lead to direct effects on gene transcription, RNA formation, cellular growth and apoptotic death. Structurally this protein resembled the lipid kinases far more than the typical protein kinases but its functions revealed significant activity in the tyrosine kinase phosphorylation processes. [Read the Full Post]

EVEROLIMUS – TEARING mTOR CASCADES

2241 | Mar 20 2012

The mTOR pathway One of the more central proteins in the many sequences of pathways that regulate growth patterns in cellular system is the “mammalian target for rapamycin”. Discovered by accident during the screening of extracts from plant and bacterial origin for biological activity this protein has proved to be highly complex in its activity. In an initial investigation it was demonstrated that this protein was essential for life itself, murine models mutated to silence this protein genetically did not survive the embryonic stage. Structurally this protein resembles a lipid kinase but it also demonstrates significant functions similar to the protein kinase super families. This protein contains more than one binding domain demonstrating kinase activity. These domains can bind with several possible ligands which trigger several different pathways. The mTOR protein can initiate scaffold building for DNA repair, to regulate other pathways in gene transcription and growth processes and regulate its own activity. mTOR signaling can be indirect as a results of a pathway trigger but also direct from extracellular signals. [Read the Full Post]

TEMSIROLIMUS

1607 | Mar 20 2012

TEMSIROLIMUS AND mTOR INHIBITORS: mTOR protein kinases belonging to phosphatidylinositol 3-kinase (PI3-K) which is related to the family of kinase proteins are responsible to regulate cell growth, survival, proliferation, protein synthesis, cell’s transcriptional activities and cell migration. Because of their influence on all of the above mentioned processes, targeting many of these enzymes for the treatment of various diseases is now a very valuable approach. Previously Rapamycin was found to be the most famous inhibitor belonging to category mTOR but these days another member of same family named as Temsirolimus mTOR inhibitor is also getting popularity. [Read the Full Post]

KINASE INHIBITORS TARGETTING CANCER ABERRATIONS

2186 | Mar 18 2012

Tyrosine kinases: Mechanisms and inhibition The super families of protein kinases are found extensively in mammalian tissues, they regulate most of the proliferation, differentiation, migration, apoptosis, motility and gene transcription that occurs in the life span of natural cell. One of the sub families is that of the tyrosine kinases (TK’s) which exist in a variety of forms, each triggering a signaling cascade which performs specific cellular functions. The mechanism of action TK’s is the direct phosphorylation of tyrosine amino acid in the binding domain of a protein. This action triggers an event to occur passing down a signaling cascade to effect cellular functions. TK’s can be subdivided into two families the non receptor tyrosine kinase (nrTK) and the receptor tyrosine kinase (rTK). The numbers of members in each family are 32 and 58 respectively; the rTK has been subdivided again into 20 different groups. The TK’s are involved in processes that are of considerable interest in the field of the prevention of cancer. The blocking cellular growth or the induction of apoptotic processes constitute then focus of nearly all cancer chemotherapy. In addition research has demonstrate that certain TK’s can be mutated so that they exist in a state permanent activity thereby inducing cancerous growth. [Read the Full Post]

TEMSIROLIMUS

2837 | Mar 18 2012

Introduction: mTOR inhibitiors The mTOR kinase is part of the same pathway as AKT and PI3K, this signaling pathway is a tyrosine kinase sub family of the super protein kinase family. The PI3K/AKT/mTOR signaling cascade is involved in a variety of cellular functions such as migration, growth, protein synthesis, survival and proliferation. PI3K and AKT inhibitors have all been reported as having significant potential as treatments against disorders involving cell growth, mTOR is part of the same pathway and theoretically would make a potential target for inhibition. It has also been reported that mutations in the mTOr signaling have been implicated in cardiovascular disease, cancer and disorders of the metabolism. Rapamycin was the first mTOR inhibitor to be released but was quickly followed by a 2nd generation analogue Sirolimus. Temsirolimus is a 3rd generation molecule designed to be an improvement over rapamycin and Sirolimus. Temsirolimus has demonstrated potential in the treatment of renal carcinomas, NSCLC and malignant glioma. [Read the Full Post]

RAPAMYCIN

2330 | Mar 18 2012

Introduction: The mTOR pathway Rapamycin is a molecule which was discovered as a byproduct of bacterial action in a soil sample from Easter Island. During extract screening it was observed that this molecule specifically targeted a previously unknown protein. This protein was purified and characterized in an intensive series of research programs. The name given to this protein was the acronym mTOR (meaning “mammalian Target for Rapamycin”). The importance of this molecule was slowly uncovered as it demonstrated significant regulatory abilities in gene transcription and cellular growth processes. The unusual aspect of this protein was its structural resemblance to the lipid kinases but its multi faceted functions similar to the serine/threonine kinases. Multiple domains were identified which responded to ligands directly from the extracellular systemic circulation and from indirect triggers from other pathways. Triggers initiated by Rapamycin mTOR inhibitor lead to adaptation of other mechanisms, building of scaffolds for DNA repair, actin organization, initiation of the start codon (AUG) in gene transcription and to regulate its own activity. [Read the Full Post]

RAD001 – Everolimus by another name

2517 | Mar 18 2012

The mTOR pathway In clinical terms the mTOR protein was one of the most significant discovers in recent times. This protein similar in nature to the lipid kinases exhibits multi-domain serine/threonine kinase activity, by binding to a series of cellular and extracellular ligands functions of cellular growth and gene transcription are regulated. Ligands that can initiate mTOR activity include growth factors such as insulin and phorbol 12-myristate 13-acetate (PMA). Effects of activation can include the regulation of DNA repair, modification of cellular growth activities, regulation of its own activity and trigger cascades in the downstream pathways. [Read the Full Post]

BEZ235: THE FIRST PI3K INHIBITOR INTO CLINICAL TRIALS

2768 | Mar 19 2012

Introduction: PI3K inhibition Currently in clinical testing are inhibitors of both Akt and mTOR which have shown significant promise for certain patient sub-populations. However, resistance and toxicity to these molecules is common, hence new targets are continuously being investigated. Upstream of Akt and mTOR is the membrane bound protein PI3K which intercepts signals from extracellular growth factor from transmission into the cytosole and eventually the nucleus. While being an upstream target PI3K is still being investigated for anti-tumor effects. PI3K is classified into several classes with class 1 being the focus of the small molecule inhibitors currently in preclinical and clinical testing. Class 1 kinases are subdivided into four different proteins containing a common catalytic domain, they are identified as Alpha, Beta, Gamma and Delta. BEZ235 PI3K inhibitor is a pan- inhibitor of all the isoforms of PI3K as well as targeting mTOR directly as well. BEZ235 is known as an effective dual inhibitor of many tumor types. [Read the Full Post]

AKT INHIBITORS AGAINST TUMOR GROWTH

4698 | Mar 13 2012

AKT PATHWAY AND ITS LINK WITH CANCERS: With the emergence of the tyrosine kinase inhibitors attention was directed toward Akt, a serine/ threonine kinase of the protein kinase family. Akt is more formally known as protein kinase B and exists in three isoforms. Its role in the cellular signaling cascades has been well documented with downstream effects on mTOR, BAD and GSK3 The PI3K/Akt/mTOR pathway has been established as having an important role in apoptosis, cell migration and proliferation, transcription and glucose metabolism. In various known forms of malignancies Akt has been established as playing a crucial role, an elevated expression of phosphorylated Akt is a contraindication of survival. Hence focus was placed on the development of AKT inhibitor drugs. AKT inhibition has been achieved with Perifosine, MK-2206, RX-0201, Erucylphosphocholine (ErPC), PBI-05204, GSK690693, A-443654 and XL-418. [Read the Full Post]

GSK3 and Alzheimer’s disease

6685 | Nov 24 2011

Glycogen synthase kinase 3 (GSK-3), as a serine/threonine protein kinase, can contribute to phosphorylating and thus inactivating glycogen synthase, and also been involved in the control of cellular response to damaged DNA. [Read the Full Post]

MK-2206, as an Akt Inhibitor, enhances antitumor efficacy by chemotherapeutic agents

3837 | Nov 17 2011

Development and maintenance of many tumors have been reported to be associated with abnormal activation of PI3K. Akt is a critical downstream factor of PI3K signaling pathway and is important in promoting cell survival and inhibiting apoptosis. Clinically, Akt activation and overexpression is often associated with resistance to chemotherapy or radiotherapy. Thus, clinically available small-molecule inhibitors of Akt have remarkable potential in cancer treatment. [Read the Full Post]

Co-treatment of PI3K inhibitors with temsirolimus, an optimized therapy in the treatment of cancers related to mTORs.

2903 | Nov 08 2011

The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that mediates cell growth, cell proliferation, cell motility, cell survival, gene transcription, and protein synthesis. In many human cancers, particularly those with loss of the tumor suppressor PTEN, dysregulation of the mTOR signaling can be observed, and activation of mTORs have shown the significant sensitivity to rapamycin. [Read the Full Post]

Roles of PI3Ks in tumors

2974 | Nov 07 2011

Phosphatidylinositol 3-kinases (PI3Ks) are a family of enzymes involved in a variety of cellular functions including cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, and the effects are considered to be implemented through regulating the activities of a broad range of downstream molecular effectors. Since phosphorylation of PI3K-AKT-mTOR inhibits the activity of proapoptotic members while activating anti-apoptotic members, and is considered to play an important role in cancer stem cell self-renewal and resistance to chemotherapy or radiotherapy. [Read the Full Post]

Boosani “Endogenous angiogenesis inhibitors affecting cell survival pathways”

2724 | Sep 13 2011

Phosphatidylinositol 3-kinases (PI3 kinases) are a group of enzymes categorized into three different classes, among them class I isoforms are well characterized (Stein, 2001). These kinases are the key enzymes that are vital for cell survival with essential role in several cellular functions such as growth, proliferation, differentiation, motility, and intracellular signaling. PI3 Kinases are activated by tyrosine kinases with Akt being the downstream effector molecule (Hennessy et al., 2005). [Read the Full Post]

PI3K/Akt inhibition modulates multidrug resistance

4962 | Sep 05 2011

Multidrug resistance (MDR), characterized by cancer cell resistance to multiple chemotherapeutic drugs, is a major clinical obstacle in the treatment of hematological malignancies. And many investigators have comfirmed that the PI3K/Akt pathway is associated with chemoresistance in cancer cells. [Read the Full Post]

Kong, X., Y. Shen, et al. (2011). "Emerging roles of DNA-PK besides DNA repair." Cell Signal 23(8): 1273-1280.

5168 | Aug 19 2011

This article reviews the role of DNA-PK from two aspects. It not only introduces the regulation of DNA-PK activity and the roles of DNA-PK in non-homologous end-joining (NHEJ) repair and homologous recombinant (HR) repair, but also introduces the involvement of DNA-PK in the inflammatory response, in metabolic gene regulation, and in the homeostasis of cell proliferation as well. [Read the Full Post]

Wong, K. K., J. A. Engelman, et al. (2010). "Targeting the PI3K signaling pathway in cancer." Curr Opin Genet Dev 20(1): 87-90.

2615 | Jul 16 2011

This is a short review which gives a brief introduction of PI3K and PI3K inhibitors related to cancer research. [Read the Full Post]

Eldar-Finkelman, H., A. Licht-Murava, et al. (2010). "Substrate competitive GSK-3 inhibitors - strategy and implications." Biochim Biophys Acta 1804(3): 598-603.

4472 | Jul 11 2011

A short article introduces the substrates and inhibitors of GSK-3 and the relationship between substrates of GSK-3 and GSK-3. [Read the Full Post]

Chin, Y. R. and A. Toker (2009). "Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer." Cell Signal 21(4): 470-476.

3479 | Jun 23 2011

This article gives an introduction of akt signal pathway in cell motility, invasion and the tumor stroma in cancer. We can learn this overview of relationship between Akt and cancer. [Read the Full Post]

Jiang, B. H. and L. Z. Liu (2008). "PI3K/PTEN signaling in tumorigenesis and angiogenesis." Biochim Biophys Acta 1784(1): 150-158.

2369 | Jun 5 2011

This review give the introduction of PI3K pathway and PI3k inhibitors for cancer research. [Read the Full Post]

Soulard, A. and M. N. Hall (2007). "SnapShot: mTOR signaling." Cell 129(2): 434.

2239 | May 13 2011

A wonderful snapshot of mTOR signaling pathway provides a picture of mTOR signaling pathway with detail information about pathway. [Read the Full Post]

Burma, S. and D. J. Chen (2004). "Role of DNA-PK in the cellular response to DNA double-strand breaks." DNA Repair (Amst) 3(8-9): 909-918.

4812 | May 11 2011

This review introduces DNA-PK as a kinase in the cellular response to DNA double-strand breaks with many details including autophosphorylation of DNA–PKcs, role of DNA–PK in the signaling of DNA damage, and the manifold functions of DNA–PK at the mammalian telomere. I t also mentions the innate immune response which DNA-PK is related to. [Read the Full Post]

Yap, T. A., M. D. Garrett, et al. (2008). "Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises." Curr Opin Pharmacol 8(4): 393-412.

3404 | Apr 4 2011

This review is about the drug discovery of cancer which is targeting the PI3K-AKT-mTOR pathway. Basic knowledge of the PI3K-AKT-mTOR pathway and anticancer therapeutics are both in this article. Anyone who is interested in drug discovery can benefit after reading this article. [Read the Full Post]

Doble, B. W. and J. R. Woodgett (2003). "GSK-3: tricks of the trade for a multi-tasking kinase." J Cell Sci 116(Pt 7): 1175-1186.

4297 | Mar 20 2011

This article introduces the insights of GSK-3 phosphorylation from crystal structures. It also introduces the role of GSK-3 in human disease, the role of GSK-3 in the Hedgehog pathway, the role of GSK-3 in the Wnt/beta-catenin pathway, GSK-3-binding proteins, GSK-3 substrates, and small molecule inhibitors of GSK-3. [Read the Full Post]