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PI3K/Akt/mTOR

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

3 | 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

17 | 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]

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

7 | Jul 31 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]

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

6 | 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

12 | 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

54 | 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

24 | 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

40 | 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

30 | 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

68 | 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

69 | 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

47 | 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

48 | 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

61 | 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

76 | 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

68 | 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

84 | 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

65 | 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

77 | 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

72 | 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

51 | 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

102 | 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

91 | 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

144 | 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

122 | 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

103 | 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

97 | 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

46 | 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

57 | 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

78 | 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

91 | 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

156 | 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

145 | Feb 13 2019

Huang H et al. suggested that mTOR inhibition may not be able to alleviate iron-induced neurotoxicity. [Read the Full Post]

Leukotriene B₄ Metabolism and p70S6 Kinase 1 Inhibitors: PF-4708671 but Not LY2584702 Inhibits CYP4F3A and the ω-Oxidation of Leukotriene B₄ In Vitro and In Cellulo

97 | Feb 10 2019

Archambault AS et al. showed that PF-4708671 inhibits CYP4F3A and prevents the ω-oxidation of LTB4 in cellulo, which might result in increased LTB4 levels in vivo. [Read the Full Post]

Sulfoximines as ATR inhibitors: Analogs of VE-821

156 | 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

157 | 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

193 | 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

178 | 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

217 | 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

484 | 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

262 | 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

190 | 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

187 | 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

293 | 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

317 | 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

114 | 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

193 | 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

136 | 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

197 | 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

130 | 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

167 | 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

140 | 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

185 | 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

281 | 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

124 | 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

165 | 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

254 | 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]

Reactivation of the p90RSK-CDC25C Pathway Leads to Bypass of the Ganetespib-Induced G2-M Arrest and Mediates Acquired Resistance to Ganetespib in KRAS-Mutant NSCLC

179 | Nov 02 2018

Chatterjee S et al. showed protective effects in OVX-induced OA partly through the TGF-β1 pathway. [Read the Full Post]

Pro-survival signal inhibition by CDK inhibitor dinaciclib in Chronic Lymphocytic Leukaemia

435 | 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

340 | 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

597 | 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

163 | 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

374 | 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

597 | 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

584 | 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

213 | 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

240 | 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

1098 | 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

635 | 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

252 | 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

322 | 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

310 | 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

292 | 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

449 | 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

424 | 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

299 | 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

556 | 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

257 | 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]

The afatinib resistance of in vivo generated H1975 lung cancer cell clones is mediated by SRC/ERBB3/c-KIT/c-MET compensatory survival signaling

594 | 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

1092 | 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

838 | 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

360 | 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

429 | 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

562 | 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

1732 | 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

632 | 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

315 | 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

573 | 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

509 | 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

582 | 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

876 | 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

582 | 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

2628 | 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

345 | 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

340 | 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]

Increased translocation of antigens to endosomes and TLR4 mediated endosomal recruitment of TAP contribute to nicotine augmented cross-presentation

370 | May 09 2018

Wang YY et al. suggested that increased recruitment of TAP to Ag-containing vesicles contributes to the superior cross-presentation efficacy of α7 nAchR activated DCs. [Read the Full Post]

Anandamide Suppresses Proinflammatory T Cell Responses In Vitro through Type-1 Cannabinoid Receptor-Mediated mTOR Inhibition in Human Keratinocytes

364 | May 08 2018

Chiurchiù V et al. demonstrated that AEA suppresses highly pathogenic T cell subsets through CB1-mediated mammalian target of rapamycin inhibition in human keratinocytes. Thus, it can be speculated that the latter pathway might be beneficial to the physiological function of the skin, and can be targeted toward inflammation-related skin diseases. [Read the Full Post]

Co-occurring Mutations of Tumor Suppressor Genes, LATS2 and NF2, in Malignant Pleural Mesothelioma

664 | 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

1379 | 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

1465 | 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

505 | 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

1622 | 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

1185 | 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

975 | 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]

Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma

0 | Mar 27 2018

Ezell SA et al. indicated that 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]

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response

0 | Mar 27 2018

Luo Y et al. identified Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response. [Read the Full Post]

Intestinal Microbiota-Derived GABA Mediates Interleukin-17 Expression during Enterotoxigenic Escherichia coli Infection

481 | Mar 26 2018

Ren W et al. highlight the importance of intestinal GABA signaling in intestinal IL-17 expression during intestinal infection and indicate the potential of intestinal microbiota-GABA signaling in IL-17-associated intestinal diseases. [Read the Full Post]

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

618 | 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

593 | 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

383 | 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

739 | 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

522 | 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

634 | 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

758 | 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

1039 | 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

968 | 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

376 | 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

405 | 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

863 | 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

750 | 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

388 | 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

837 | 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

686 | 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

659 | 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

1054 | 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

555 | 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

726 | 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

652 | 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

1234 | 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

1222 | 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

452 | 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

684 | 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

738 | 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

693 | 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

1160 | 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

753 | 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

755 | 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

793 | 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

950 | 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

833 | 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

680 | 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

615 | 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

569 | 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

985 | 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

893 | 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

2075 | 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

590 | 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

724 | 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

720 | 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

652 | 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

656 | 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

844 | 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

1119 | 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

2395 | 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

1208 | 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

2181 | 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

1699 | 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

1770 | 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

2538 | 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

1915 | 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.

1877 | 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

1084 | 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

1301 | 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

1422 | 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

1389 | 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.

2953 | 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

1196 | 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

1142 | 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.

1092 | 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

1368 | 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

1213 | 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

956 | 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

1058 | 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

2470 | 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.

2575 | 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

781 | 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

943 | 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

673 | 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

5860 | 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

952 | 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

667 | 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

1088 | 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

937 | 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

808 | 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

1368 | 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

1068 | 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

884 | 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

880 | 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

3062 | 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

2106 | 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

1402 | 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

1035 | 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

1060 | 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

1281 | 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

1098 | 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

1228 | 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

911 | 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

1483 | 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

2267 | 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.

1004 | 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

1246 | 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

1227 | 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.

1664 | 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

1546 | 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

1093 | 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

2182 | 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

2121 | 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

1739 | 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

1524 | 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.

1451 | 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

1083 | 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

2110 | 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

1786 | 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

1930 | 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

1713 | 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

1089 | 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

1744 | 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

1650 | 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

2260 | 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

1356 | 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

1029 | 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

1380 | 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

1844 | 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

1148 | 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

1860 | 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

1690 | 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

2424 | 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

1700 | 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

1666 | 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

1804 | 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

1624 | 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

1757 | 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

1168 | 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

1615 | 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

1836 | 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

6368 | 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

3598 | 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

2805 | 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

5331 | 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

4892 | 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

6959 | 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

4950 | 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

9789 | 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

4816 | 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

2365 | 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

3692 | 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

8240 | 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

1938 | 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

2423 | 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

4570 | 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

5822 | 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

3889 | 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

7307 | 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

2700 | 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

2151 | 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

1898 | 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

2199 | 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

2053 | 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

3351 | 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

2913 | Mar 05 2014

Perifosine combining with temozolomide reduces tumor proliferation in vivo. [Read the Full Post]

Wortmannin is a specific covalent inhibitor of PI3K

1995 | 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

1941 | 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

1977 | 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

2032 | 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

1959 | 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

2111 | 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

2947 | 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

2286 | 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

1671 | 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

2265 | 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

3021 | 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

1899 | 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

2088 | 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

2144 | 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

3123 | 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

1641 | 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

1834 | 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

1971 | 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

1722 | 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

2043 | 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

3776 | 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

1876 | 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

2256 | 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

2325 | 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

1907 | 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

3760 | 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

1850 | 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

3047 | 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

1794 | 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

3385 | 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

3818 | 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

2967 | 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

1811 | 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

2343 | 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

3708 | 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

2390 | 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

1961 | 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

1441 | 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

3340 | 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

3440 | 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

3305 | 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

3176 | 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

6198 | 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

5836 | 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

4242 | 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

9431 | 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

6932 | 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

3601 | 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

6342 | 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

2539 | 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

3259 | 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

2538 | 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

7232 | 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

3208 | 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

2330 | 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

3513 | 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

3217 | 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

2911 | 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

3615 | 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

2752 | 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

2932 | 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

2688 | 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

3099 | 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

2280 | 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

2614 | 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

2473 | 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

2644 | 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

2748 | 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

2139 | 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

2339 | 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

2056 | 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

2052 | 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

3316 | 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

2262 | 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

1671 | 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

2218 | 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

2085 | 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

1958 | 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

1352 | 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

1904 | 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

2284 | 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

1820 | 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

2204 | 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

2412 | 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

3929 | 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

5614 | 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

3188 | 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.

2455 | 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

2636 | 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]

S6K and PDK1 modulate neuronal size specification

5805 | Sep 22 2011

Synapse is located in the nervous system and a structure that passes an electrical or chemical signalfrom a neuron to another cell. The presynaptic terminal is a specialized area within the axon of the presynaptic cell that contains neurotransmitters enclosed in small membrane-bound spheres called synaptic vesicles. Active zones is a region that synaptic vesicles are docked at the presynaptic plasma membrane. [Read the Full Post]

Boosani “Endogenous angiogenesis inhibitors affecting cell survival pathways”

2414 | 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

4454 | 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.

4552 | 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.

2248 | 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.

4047 | 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.

3021 | 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.

2051 | 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.

1924 | 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.

4290 | 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.

2975 | 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.

3824 | 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]