Category

Archives

Cell Cycle

Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines

1 | Nov 27 2020

Carmelina Antonella Iannuzzi et al. suggested that the dl922-947-AZD1775 combination could be a feasible strategy against MM. [Read the Full Post]

An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

2 | Nov 22 2020

Sunita Shankar et al. supported a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR-RAS signaling, and an AGO2-dependent phase wherein the mutant KRAS-AGO2 interaction was critical for PDAC progression. [Read the Full Post]

Identification of Quinazolinone Analogs Targeting CDK5 Kinase Activity and Glioblastoma Cell Proliferation

6 | Nov 12 2020

Marion Peyressatre et al. found that the quinazolinone derivatives were the first small molecules reported to target CDK5 at a site other than the ATP pocket, thereby constituting attractive leads for glioblastoma therapeutics and providing therapeutic perspectives for neurodegenerative diseases. [Read the Full Post]

Ginsenoside Rg1 reduces β‑amyloid levels by inhibiting CDΚ5‑induced PPARγ phosphorylation in a neuron model of Alzheimer's disease

3 | Nov 12 2020

Qiankun Quan et al. suggested that ginsenoside Rg1 had neuroprotective properties and had potential for use in the treatment of AD. [Read the Full Post]

Optimization and Evaluation of Propolis liposomes as a promising therapeutic approach for COVID-19

10 | Nov 11 2020

Hesham Refaat et al. identified the potential of propolis liposomes as a promising treatment approach against COVID-19. [Read the Full Post]

The CHK1 inhibitor MU380 significantly increases the sensitivity of human docetaxel-resistant prostate cancer cells to gemcitabine through the induction of mitotic catastrophe

8 | Nov 09 2020

Stanislav Drápela et al. suggested that metabolically robust and selective CHK1 inhibitor MU380 could bypass docetaxel resistance and improve the effectiveness of GEM in DR mCRPC models. [Read the Full Post]

Phosphoproteomics Analysis Reveals a Potential Role of CHK1 in Regulation of Innate Immunity through IRF3

8 | Nov 09 2020

Zhen Chen et al. indicated that the CHK1-dependent regulation of IRF3 phosphorylation at S173 and S175 might play a role in the induction of innate immune response after replication stress or DNA damage, which suggested a potential function of CHK1 in the innate immune response. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

0 | Nov 06 2020

Poojabahen Tajpara et al. discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. [Read the Full Post]

Identification of antiviral compounds against equid herpesvirus-1 using real-time cell assay screening: Efficacy of decitabine and valganciclovir alone or in combination

9 | Nov 05 2020

Côme Thieulent et al. showed that deoxycytidine reverts the antiviral effect of decitabine, thus supporting some competition at the level of nucleoside phosphorylation by deoxycytidine kinase and/or DNA synthesis. [Read the Full Post]

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

18 | Oct 29 2020

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

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

19 | Oct 27 2020

E M Samoilova et al. found that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells

12 | Oct 16 2020

Svenja Wiechmann et al.improved the understanding of radioresistance and provided avenues for developing radiotherapeutic strategies. [Read the Full Post]

An exon skipping screen identifies antitumor drugs that are potent modulators of pre-mRNA splicing, suggesting new therapeutic applications

16 | Oct 14 2020

Yihui Shi et al.supported the broad potential for the development of agents that targeted the spliceosome for the treatment of cancer and other diseases, as well as new avenues for the discovery of new chemotherapeutic agents for a range of diseases. [Read the Full Post]

A study of human leukocyte antigen-haploidentical hematopoietic stem cells transplantation combined with allogenic mesenchymal stem cell infusion for treatment of severe aplastic anemia in pediatric and adolescent patients

37 | Sep 29 2020

Li Ding et al. suggested that cotransplantation of HLA-haploidentical HSC and allogenic mesenchymal stem cell might provide an effective and safe treatment for children and adolescents with SAA who lacked matched donors. [Read the Full Post]

CTELS: A Cell-Free System for the Analysis of Translation Termination Rate

30 | Sep 28 2020

Kseniya A Lashkevich et al. revealed a transient stalling event at a "leaky" stop codon context, which likely defined the basis of nonsense suppression. [Read the Full Post]

Phase Ib Study of Ribociclib Plus Fulvestrant and Ribociclib Plus Fulvestrant Plus PI3K-Inhibitor (Alpelisib or Buparlisib) for HR+ Advanced Breast Cancer

20 | Sep 23 2020

Sara M Tolaney et al .showed that Ribociclib plus fulvestrant demonstrated safety in the treatment of patients with HR+, HER2- ABC. [Read the Full Post]

Inhibition of Aurora Kinase B attenuates fibroblast activation and pulmonary fibrosis

26 | Sep 21 2020

Rajesh K Kasam et al. provided important proof-of-concept that demonstrated barasertib as a possible intervention therapy for IPF. [Read the Full Post]

Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets

23 | Sep 21 2020

Julia Krushkal et al. indicated potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggested targets for combination therapies. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

106 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

The rRNA synthesis inhibitor CX-5461 may induce autophagy that inhibits anticancer drug-induced cell damage to leukemia cells

30 | Aug 18 2020

Shuichiro Okamoto et al. showed the autophagy which might be induced by CX-5461 was the second type. [Read the Full Post]

Antiviral activity of PLK1-targeting siRNA delivered by lipid nanoparticles in HBV-infected hepatocytes

68 | Aug 10 2020

Adrien Foca et al. emphasized that a specific PLK1 inhibition could help in achieving an improved HBsAg loss in CHB patients, likely in combination with other HBsAg-targeting strategies. [Read the Full Post]

Gemcitabine combined with cisplatin vs. taxane, cisplatin, and fluorouracil in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective case-control study

81 | Aug 04 2020

Y-M Huang et al. showed that the clinical efficacy of the GP regimen combined with CCRT for the treatment of locoregionally advanced NPC might be better than that of the TPF regimen. [Read the Full Post]

The Apparent Requirement for Protein Synthesis during G2 Phase Is due to Checkpoint Activation

44 | Jul 29 2020

Sarah Lockhead et al. showed that protein synthesis during G2 phase was not required for mitotic entry, at least when the p38 checkpoint pathway was abrogated. [Read the Full Post]

Polo-like kinase 1 as a promising diagnostic biomarker and potential therapeutic target for hepatocellular carcinoma

76 | Jul 22 2020

Eman H Yousef et al. found that Polo-like kinase 1 might be a potential biomarker for hepatocellular carcinoma diagnosis and follow-up during treatment with chemotherapies. [Read the Full Post]

DrugSniper, a Tool to Exploit Loss-Of-Function Screens, Identifies CREBBP as a Predictive Biomarker of VOLASERTIB in Small Cell Lung Carcinoma (SCLC)

68 | Jul 21 2020

Fernando Carazo et al. showed the potential of genome-wide loss-of-function screens to identify new personalized therapeutic hypotheses in SCLC and potentially in other tumors, which was a valuable starting point for further drug development and drug repositioning projects. [Read the Full Post]

Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial

100 | Jul 17 2020

Andrew M Brunner et al. suggested that alisertib combined with induction chemotherapy is active and safe in previously untreated patients with high-risk acute myeloid leukaemia. [Read the Full Post]

Cyclin-Dependent Kinase 4/6 Inhibitors Combined With Radiotherapy for Patients With Metastatic Breast Cancer

55 | Jul 08 2020

Ivica Ratosa et al. observed a modest increase in the rates of grade 3 or higher AEs after combined RT and CDK4/6i, with maintained efficacy of concomitant RT. [Read the Full Post]

Inhibition of Aurora Kinase A by Alisertib Reduces Cell Proliferation and Induces Apoptosis and Autophagy in HuH-6 Human Hepatoblastoma Cells

105 | Jun 19 2020

Jingyi Tan et al. suggested that AURKA may be a novel therapeutic target and ALS a potential therapeutic drug for the treatment of HB. [Read the Full Post]

Prediction of Therapeutic Outcome and Survival in a Transgenic Mouse Model of Pancreatic Ductal Adenocarcinoma Treated With Dendritic Cell Vaccination or CDK Inhibitor Using MRI Texture: A Feasibility Study

108 | Jun 17 2020

Aydin Eresen et al. demonstrated that MRI texture features had great potential to generate diagnosis and prognosis models for monitoring early treatment response following dinaciclib drug or DC vaccine treatment and also predicting histopathological tumor markers and long-term clinical outcomes. [Read the Full Post]

Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2

107 | Jun 16 2020

Erik B Faber et al. detailed the positive cooperativity between ANS and orthosteric Cdk2 inhibitors dinaciclib and roscovitine, which increased the affinity of ANS toward Cdk2 5-fold to 10-fold, and the relatively noncooperative effects of ATP. [Read the Full Post]

Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor: A Review of Pharmacodynamics and Clinical Development

0 | May 21 2020

Amy S Clark et al. found that Palbociclib was well tolerated and had therapeutic potential for multiple cancers, including breast cancer, where its efficacy had been demonstrated alone and in combination with endocrine therapy. [Read the Full Post]

Inhibition of Rb phosphorylation leads to H2S-mediated inhibition of NF-kB in acute pancreatitis and associated lung injury in mice

78 | May 17 2020

Sundar V et al. revealed a novel link between H2S/RB/NF-κB pathways, in AP and provided insight into possible mechanism that can be targeted in prevention of inflammation to cancer development. [Read the Full Post]

Glucagon-like peptide 1 reverses myocardial hypertrophy through cAMP/PKA/RhoA/ROCK2 signaling.

155 | May 14 2020

Fan S et al. suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway. [Read the Full Post]

The Rho-associated kinase inhibitor fasudil can replace Y-27632 for use in human pluripotent stem cell research

259 | May 12 2020

So S et al. suggested that fasudil can replace Y-27632 for use in stem research. [Read the Full Post]

RO-3306 prevents postovulatory aging-mediated spontaneous exit from M-II arrest in rat eggs cultured in vitro

76 | May 04 2020

Prasad S et al. resulted suggest that postovulatory aging destabilizes MPF by modulating specific phosphorylation of Cdk1 and cyclin B1 level. RO-3306 prevented these changes and maintained M-II arrest in rat eggs cultured in vitro. Hence, maintenance of M-II arrest in ovulated eggs using RO-3306 could be beneficial to increase the number of eggs available for various ART programs. [Read the Full Post]

Covalent CDK7 Inhibitor THZ1 Inhibits Myogenic Differentiation

80 | Apr 27 2020

Xinqi Ma et al. indicated that THZ1 inhibits myogenic differentiation, suggesting that therapies based on THZ1 might have potential side effects on muscle functions. [Read the Full Post]

Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4

95 | Apr 14 2020

Mills SC et al. suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand. [Read the Full Post]

A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients

95 | Apr 13 2020

Laquente B et al. showed that LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer. [Read the Full Post]

Effects of a checkpoint kinase inhibitor, AZD7762, on tumor suppression and bone remodeling

89 | Apr 12 2020

Wang L et al. indicated that in addition to acting as a tumor suppressor, AZD7762 may prevent bone loss by inhibiting osteoclastogenesis and stimulating osteoblast mineralization. [Read the Full Post]

Prexasertib treatment induces homologous recombination deficiency and synergizes with olaparib in triple-negative breast cancer cells

101 | Apr 07 2020

Mani C et al. indicted that RAD51 could be a biomarker for aggressive TNBC and for racial disparity in breast cancer. As positive correlation exists between RAD51 and CHEK1 expression in breast cancer, the in vitro preclinical data presented here provides additional mechanistic insights for further evaluation of the rational combination of prexasertib and olaparib for improved outcomes and reduced racial disparity in TNBC. [Read the Full Post]

CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib

97 | Apr 07 2020

Sen T et al. provided a preclinical proof of concept supporting the initiation of a clinical efficacy trial in patients with platinum-sensitive or platinum-resistant relapsed SCLC. [Read the Full Post]

Orthotopic patient-derived xenografts of paediatric solid tumours

87 | Apr 06 2020

Stewart E et al. identified several drug vulnerabilities and showed that the combination of a WEE1 inhibitor (AZD1775), irinotecan, and vincristine can lead to complete response in multiple rhabdomyosarcoma orthotopic patient-derived xenografts tumours in vivo. [Read the Full Post]

Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer

93 | Mar 31 2020

Molina-Arcas M et al. provided a rationale for the design of combination treatments to enhance the impact of the KRAS-G12C inhibitors, which are now entering clinical trials. [Read the Full Post]

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

96 | Mar 14 2020

Zheng H et al. demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. [Read the Full Post]

Targeting KRAS Mutant Cancers With a Covalent G12C-Specific Inhibitor

114 | Feb 17 2020

Matthew R Janes et al. provided in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRASG12C-specific inhibitors with promising therapeutic potential. [Read the Full Post]

Rho-kinase ROCK inhibitors reduce oligomeric tau protein

259 | Feb 10 2020

Hamano T et al. suggested that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease. [Read the Full Post]

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive Her2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

97 | Feb 08 2020

Demir A et al. demonstrated that the efficacy of palbociclib among heavily treated hormone receptor-positive/HER2-negative advanced BC patients was acceptable clinical benefit, and it was generally well tolerated among this population. [Read the Full Post]

Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

103 | Jan 27 2020

Khalil HS et al. argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division. [Read the Full Post]

Tumor-Directed Therapeutic Targets in Cushing Disease

131 | Jan 27 2020

Theodoropoulou M et al. indicated that for many patients with CD, effective tumor-targeted pharmacological therapy is still lacking. Coordinated efforts are pivotal in establishing efficacy and safety of novel therapeutics in this rare but devastating disease. [Read the Full Post]

Protective effect of roscovitine against rotenone-induced parkinsonism

107 | Jan 26 2020

Chen Y et al. indicated that mouse models of Parkinson's disease were established by oral rotenone administration and reproduced some of the features of dopaminergic neuronal degeneration. Roscovitine protects against rotenone-induced parkinsonism. [Read the Full Post]

Chk1 inhibitor SCH 900776 enhances the antitumor activity of MLN4924 on pancreatic cancer

0 | Jan 22 2020

Li JA et al. provided the preclinical evidence and the rationale of the combination therapy of MLN4924 with SCH 900776 or other Chk1 inhibitors to treat PC. [Read the Full Post]

CDK4/6 Inhibitor Palbociclib Amplifies the Radiosensitivity to Nasopharyngeal Carcinoma Cells via Mediating Apoptosis and Suppressing DNA Damage Repair

141 | Jan 16 2020

Xie X et al. demonstrated that palbociclib could provoke a strong antitumor activity as a potential adjuvant to radiation therapy for NPC harboring RB expression. [Read the Full Post]

MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor cells

119 | Jan 15 2020

Bridges KA et al. indicated that MK-8776 radiosensitizes tumor cells by mechanisms that include abrogation of the G2 block and inhibition of DSB repair. Our findings support the clinical evaluation of MK-8776 in combination with radiation. [Read the Full Post]

Efficacy of pritelivir and acyclovir in the treatment of herpes simplex virus infections in a mouse model of herpes simplex encephalitis

128 | Jan 13 2020

Quenelle DC et al. concluded pritelivir has potent and resistance-breaking antiviral efficacy with potential for the treatment of potentially life-threatening HSV type 1 and 2 infections, including herpes simplex encephalitis. [Read the Full Post]

Preparation and evaluation of 99mTc-labeled HYNIC-palbociclib analogs for cyclin-dependent kinase 4/6-positive tumor imaging

101 | Jan 11 2020

Gan Q et al. indicated that 99mTc-tricine-TPPTS-L is a promising tumor imaging agent that targets CDK4/6. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

0 | Jan 03 2020

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

Targeting the cell cycle in head and neck cancer by Chk1 inhibition: a novel concept of bimodal cell death

110 | Dec 22 2019

van Harten AM et al. concluded that Chk1 has become a key molecule in HNSCC cell cycle regulation and a very promising therapeutic target. Chk1 inhibition leads to S-phase apoptosis or death in mitosis. We provide a potential efficacy biomarker and combination therapy to follow-up in clinical setting. [Read the Full Post]

Reactive oxygen species generation and increase in mitochondrial copy number: new insight into the potential mechanism of cytotoxicity induced by aurora kinase inhibitor, AZD1152-HQPA

198 | Dec 13 2019

Zekri A et al. showed a functional relationship between the aurora kinase inhibition, an increase in mitochondrial copy number, and ROS generation in therapeutic modalities of cancer. This study suggests that the excessive ROS generation may be a novel mechanism of cytotoxicity induced by the aurora kinase inhibitor, AZD1152-HQPA. [Read the Full Post]

Fludarabine-PET in a murine model of multiple myeloma

306 | Dec 08 2019

Hovhannisyan N et al. suggested that [18F]fludarabine-PET might represent an alternative and perhaps more specific modality for MM imaging when compared to [18F]FDG. Nevertheless, more investigations are required to extend this conclusion to humans. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

0 | Dec 06 2019

Yoshinari T et al. indicated that the inhibitory activity of BcS against aflatoxin production was enhanced by esterification of its carboxyl group and that the carboxymethyl ester derivative might be more suitable for practical use than BcS because of the specificity of the carboxymethyl ester derivative, which inhibited aflatoxin production more than BcS. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

0 | Nov 28 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

0 | Oct 29 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016). [Read the Full Post]

BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1

182 | Oct 19 2019

Gohda J et al. found that BI-2536 synergistically activates the latent provirus in combination with SAHA, a histone deacetylase inhibitor, or the non-tumour-promoting phorbol ester prostratin. Our findings strongly suggest that BI-2536 and BI-6727 are potent LRAs for the "shock and kill" HIV-1 eradication strategy. [Read the Full Post]

The Herb-Drug Pharmacokinetic Interaction of 5-Fluorouracil and Its Metabolite 5-Fluoro-5,6-Dihydrouracil with a Traditional Chinese Medicine in Rats

167 | Oct 17 2019

Liu JH et al. indicated the pharmacokinetic results confirm the safety of coadministering 5-FU with XSLJZT, and provide practical dosage information for clinical practice. [Read the Full Post]

Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis

0 | Oct 10 2019

Chen G et al. provided a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers. [Read the Full Post]

Inhibition of Suicidal Erythrocyte Death by Volasertib

0 | Sep 30 2019

Al Mamun Bhuyan A et al. showed that Volasertib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and hyperosmotic shock, effects contrasting the stimulation of K562 cell apoptosis. [Read the Full Post]

BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity

0 | Sep 30 2019

Rudolph D et al. indicated these findings warrant further investigation of BI 6727 as a tailored antimitotic agent; clinical studies have been initiated. [Read the Full Post]

Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine

144 | Sep 18 2019

Gelbert LM et al. identified a potent, orally active small-molecule inhibitor of CDK4/6 that is active in xenograft tumors. LY2835219is currently in clinical development. [Read the Full Post]

NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway

405 | Aug 30 2019

Dér B et al. identified potential therapeutic targets of bladder dysfunctions related to upregulation of TKs. [Read the Full Post]

Functional genomics identifies predictive markers and clinically actionable resistance mechanisms to CDK4/6 inhibition in bladder cancer

160 | Aug 29 2019

Tong Z et al. found that identification of potential predictive markers, resistance mechanisms and rational combination therapies could be achieved by applying a CRISPR-dCas9 screening approach in bladder cancer. [Read the Full Post]

Alisertib demonstrates significant antitumor activity in bevacizumab resistant, patient derived orthotopic models of glioblastoma

240 | Aug 20 2019

Kurokawa C et al. showed that alisertibdisplays significant antitumor activity against primary GBM lines and xenografts, including patient derived GBM lines resistant to bevacizumab; these data support clinical translation in GBM. [Read the Full Post]

Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells

264 | Aug 20 2019

Levesley J et al. indicated that selective small-molecule inhibitors of BCL-XL may enhance the efficacy of MLN8237 and other targeted chemotherapeutic agents. [Read the Full Post]

Overview of CDK9 as a target in cancer research

165 | Aug 13 2019

Morales F et al. concluded that there are many small molecules that bind to CDK9, but their lack of selectivity against other CDKs do not allow them to get to the clinical use. However, drug designers currently have the tools needed to improve the selectivity of CDK9 inhibitors and to make successful treatment available to patients. [Read the Full Post]

Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia

0 | Aug 12 2019

Moharram SA et al. identified the CDK inhibitor dinaciclib as a potential drug for T-ALL. Dinaciclib treatment significantly reduced cell viability and completely blocked colony formation. Furthermore, cells treated with dinaciclibshowed decreased expression of several pro-survival proteins including survivin, cyclin T1 and c-MYC. Dinaciclib treatment also increased accumulation of cells in G2/M phase and significantly induced apoptosis. Finally, dinaciclib extended survival of mice in a T-ALL cell xenograft model. Collectively, these data suggest that the CDK inhibitor dinaciclib is an active drug for T-ALL in the preclinical settings. [Read the Full Post]

Palbociclib (PD0332991)-a Selective and Potent Cyclin-Dependent Kinase Inhibitor: A Review of Pharmacodynamics and Clinical Development

175 | Jul 17 2019

Clark AS et al. indicated that palbociclib is well tolerated and has therapeutic potential for multiple cancers, including breast cancer, where its efficacy has been demonstrated alone and in combination with endocrine therapy. Additional combinations of palbociclib with endocrine therapy, chemotherapy, and targeted therapy have potential in various tumors, and phase 3 trials are under way. [Read the Full Post]

Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome

421 | Jul 10 2019

Reynolds SD et al. concluded that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification. [Read the Full Post]

Characterization of Three Novel H3F3A-mutated Giant Cell Tumor Cell Lines and Targeting of Their Wee1 Pathway

208 | Jul 09 2019

Lübbehüsen C et al, offered valuable new tools for GCTB studies and presents a description of novel biomarkers and molecular targeting strategies. [Read the Full Post]

Effect of CHK1 Inhibition on CPX-351 Cytotoxicity in vitro and ex vivo

167 | Jun 10 2019

Vincelette ND et al. showed that CHK1 inhibition increases the antiproliferative effect of CPX-351 on primary AML specimens ex vivo, offering the possibility that CPX-351 may be well suited to combine with CHK1-targeted agents. [Read the Full Post]

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study

215 | Jun 09 2019

Wouda RM et al. indicated the dose-limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well-tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials. [Read the Full Post]

Inhibitory Activities of Blasticidin S Derivatives on Aflatoxin Production by Aspergillus Flavus

200 | Jun 03 2019

Yoshinari T et al. indicated that the inhibitory activity of BcS against aflatoxin production was enhanced by esterification of its carboxyl group and that the carboxymethyl ester derivative might be more suitable for practical use than BcS because of the specificity of the carboxymethyl ester derivative, which inhibited aflatoxin production more than BcS. [Read the Full Post]

KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells

455 | May 31 2019

Diep DTV et al. indicated that KD025suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. [Read the Full Post]

Chk1 inhibitor SCH 900776 enhances the antitumor activity of MLN4924 on pancreatic cancer

253 | May 28 2019

Li JA et al. provided the preclinical evidence and the rationale of the combination therapy of MLN4924 with SCH 900776 or other Chk1 inhibitors to treat PC. [Read the Full Post]

The Potential Contribution of microRNAs in Anti-cancer Effects of Aurora Kinase Inhibitor (AZD1152-HQPA)

295 | May 27 2019

Zekri A et al. showed for the first time the potential contribution of miRNAs in the anti-cancer effects of AZD1152-HQPA. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

0 | May 25 2019

Tajpara P et al. present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research. [Read the Full Post]

Suppression of Sirt1 sensitizes lung cancer cells to WEE1 inhibitor MK-1775-induced DNA damage and apoptosis

244 | May 24 2019

Chen G et al. provided a novel therapeutic strategy to optimize MK-1775 treatment efficiency in lung cancers. [Read the Full Post]

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial

507 | May 21 2019

Rummel M et al. indicated that in combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. [Read the Full Post]

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

183 | May 14 2019

Cazzaniga ME et al. proposed a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy. [Read the Full Post]

Dependency of Cholangiocarcinoma on Cyclin D-Dependent Kinase Activity

201 | May 13 2019

Sittithumcharee G et al. proposed that the CDK4/6-pRB pathway is a suitable therapeutic target for CCA treatment. This article is protected by copyright. All rights reserved. [Read the Full Post]

The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy

258 | May 09 2019

Zhou ZR et al. suggested that MK-8776increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC. [Read the Full Post]

Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo

348 | May 07 2019

Helfrich BA et al. suggested that SCLC tumors with cMYC amplification/high gene expression will frequently respond to Aurora B inhibitors and that clinical studies coupled with predictive biomarkers are indicated. [Read the Full Post]

A Preclinical Model for Studying Herpes Simplex Virus Infection

261 | Apr 29 2019

Tajpara P et al. discovered that both drugs had a comparable efficacy for inhibiting HSV-1 replication, suggesting that pritelivir could be an alternative therapeutic agent for patients infected with acyclovir-resistant strains. To our knowledge, we present a previously unreported ex vivo HSV-1 infection model with abdominal human skin to test antiviral drugs, thus bridging the gap between in vitro and in vivo drug screening and providing a valuable preclinical platform for HSV research. [Read the Full Post]

In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas

230 | Apr 28 2019

Lacrima K et al. suggested that CYC202 is an active agent in MCL. The concomitant decrease of the phosphorylated and total forms of RNA polymerase II suggests that this could be the main mechanism mediating the biological effects of CYC202 in MCL cells. The drug might represent a new therapeutic agent in this lymphoma subtype. [Read the Full Post]

Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis

216 | Apr 18 2019

Jiang ZX et al. showed that roscovitine ameliorates EIU by effecting neutrophil apoptosis. Timely apoptosis of neutrophils may be an effective process to promote the amelioration of EIU. [Read the Full Post]

Prevention of Intraabdominal Adhesions: An Experimental Study Using Mitomycin-C and 4% Icodextrin

0 | Apr 16 2019

Urkan M et al. indicated that despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials. [Read the Full Post]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

613 | Mar 27 2019

Yan H et al. suggested that the U46619-induced contraction of mouse intrarenal arteries is mediated by Cav1.2 and SOC channel, through the activation of thromboxane-prostanoid receptors and its downstream signaling pathway. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

555 | Mar 24 2019

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

Ten-Year and Beyond Follow-up After Treatment With Highly Purified Liquid-Injectable Silicone for HIV-Associated Facial Lipoatrophy: A Report of 164 Patients

204 | Mar 22 2019

Jones DH et al. showed that liquid-injectable silicone is an effective long-term treatment option for HIV-FLA. When injected in small quantities with the microdroplet serial puncture technique at monthly or greater intervals, optimal correction appears durable for more than 10 years. Adverse events consisted mostly of excess fibroplasia and were treatable. [Read the Full Post]

5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer

243 | Mar 22 2019

Morawska K et al. showed at a cycle 1, the 5-FU dose was calculated using patient's Body Surface Area (BSA) method. A blood sample was drawn on Day 2 to measure 5-FUconcentration. At cycle 2, the 5-FU dose was adjusted using a PK-guided dosing strategy targeting a plasma AUC range of 18-28 mg·h/L, based on cycle 1 concentration. Assessments of toxicity was performed at the beginning of every cycle. [Read the Full Post]

[Evolving 5-Fluorouracil Therapy to Achieve Enhanced Efficacy-Past and Current Efforts of Researchers]

194 | Mar 20 2019

Maehara Y et al. indicated that in the current standard treatment for gastrointestinal cancers, anticancer 5-FU derivatives serve as a platform for combination regimens with other cytotoxic agents or molecular- targeted drugs. To provide further improvements in anticancer therapy outcomes, novel molecular-targeted agents, immune checkpoint inhibitors, and other drugs are being developed, but 5-FU remains an attractive target that shows further potential for increased efficacy. In the future, the evolution of anticancer therapy with 5-FU derivatives is expected to continue via a variety of approaches. [Read the Full Post]

The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma

153 | Mar 18 2019

Ku BM et al. suggested that a combinational treatment with LY2835219 and mTOR inhibitor is a promising therapeutic approach for HNSCC. [Read the Full Post]

Binding of the anticancer drug BI-2536 to human serum albumin. A spectroscopic and theoretical study

264 | Mar 01 2019

Fernández-Sainz J et al. showed that the main protein-drug interactions are of the van der Waals type although the presence of amide and ether groups in BI-2536 could also allow H-bonding with some residues in the subdomain IIA pocket. [Read the Full Post]

CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours

285 | Feb 14 2019

Xu H et al. indicated these data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. [Read the Full Post]

Inhibition of Suicidal Erythrocyte Death by Volasertib

277 | Feb 04 2019

Al Mamun Bhuyan A et al. volasertib is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and hyperosmotic shock, effects contrasting the stimulation of K562 cell apoptosis. [Read the Full Post]

BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity

315 | Feb 04 2019

Rudolph D et al. showed that with oral and i.v. routes of administration, the total weekly dose of BI 6727 is most relevant for efficacy, supporting the use of a variety of well-tolerated dosing schedules. [Read the Full Post]

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer

411 | Feb 03 2019

Valle J et al. showed that as compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. [Read the Full Post]

Efficacy of the CDK inhibitor dinaciclib in vitro and in vivo in T-cell acute lymphoblastic leukemia

278 | Feb 02 2019

Moharram SA et al. suggested that the CDK inhibitor dinaciclib is an active drug for T-ALL in the preclinical settings. [Read the Full Post]

Dinaciclib (SCH727965) inhibits the unfolded protein response through a CDK1- and 5-dependent mechanism

250 | Feb 02 2019

Nguyen TK et al. highlight a link between specific components of the cell-cycle regulatory apparatus (e.g., CDK1/5) and the cytoprotective IRE1/XBP-1s/Grp78 arm of the UPR that may be exploited therapeutically in UPR-driven malignancies. [Read the Full Post]

v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1

222 | Jan 27 2019

Ju X et al. found that Cyclin D1 serves as a transducer of v-Src-mediated induction of Trop2 ICD by enhancing abundance of the Trop2 proteolytic activation complex. [Read the Full Post]

Cisplatin is retained in the cochlea indefinitely following chemotherapy

230 | Jan 17 2019

Breglio AM et al. demonstrated long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity. [Read the Full Post]

Efficacy of a bleomycin microneedle patch for the treatment of warts

270 | Jan 15 2019

Ryu HR et al. indicated the bleomycin microneedle patch can be an effective, convenient, and innovative treatment modality for warts. [Read the Full Post]

Inhibition of Chk1 with the small molecule inhibitor V158411 induces DNA damage and cell death in an unperturbed S-phase

333 | Dec 21 2018

Wayne J et al. identified two distinct classes of Chk1 inhibitors: those that induced a strong increase in γH2AX, pChk1 (S317) and pRPA32 (S4/S8) (including V158411, LY2603618 and ARRY-1A) and those that did not (including MK-8776 and GNE-900). [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells

0 | Dec 18 2018

Park GB et al. showed that characterization of the p110 isotypes of PI3K is critical for regulating cancer metastasis; LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

Leishmania donovani Aurora kinase: A promising therapeutic target against visceral leishmaniasis

439 | Dec 15 2018

Chhajer R et al. identified an Aurora kinase homolog in L. donovani implicated in cell-cycle progression, whose inhibition led to aberrant changes in cell-cycle progression and reduced viability. [Read the Full Post]

Therapeutic targeting of Polo-like kinase-1 and Aurora kinases in T-cell acute lymphoblastic leukemia

503 | Dec 13 2018

Spartà AM et al. indicated that PLK1 and AK inhibitors display the potential for being employed in innovative therapeutic strategies for improving T-ALL patient outcome. [Read the Full Post]

Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients

271 | Dec 06 2018

Prudencio M et al. concluded that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD. [Read the Full Post]

Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution

279 | Dec 02 2018

Kroon J et al. showed that flow induces Rac1 activity at the downstream side of the cell in a Trio-dependent manner and that Trio functions as a scaffold protein rather than a functional GEF under long-term flow conditions. [Read the Full Post]

Targeted inhibition of Polo-like kinase 1 by a novel small-molecule inhibitor induces mitotic catastrophe and apoptosis in human bladder cancer cells

312 | Nov 28 2018

Zhang Z et al. demonstrated of bladder cancer growth inhibition and dissemination using a pharmacological inhibitor of PLK1 provides new opportunities for future therapeutic intervention. [Read the Full Post]

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance

0 | Nov 22 2018

Löschmann N et al. showed that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. [Read the Full Post]

The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro

938 | Nov 13 2018

Shiomitsu K et al. suggested the potential usefulness of treating canine mast cell tumours with aurora kinase inhibitors alone or in conjunction with radiation therapy. [Read the Full Post]

Rac1 and Cdc42 Play Important Roles in Arsenic Neurotoxicity in Primary Cultured Rat Cerebellar Astrocytes

332 | Nov 12 2018

An Y et al. indicated that activations of Rac1 and Cdc42 play a very important role in arsenic neurotoxicity in rat cerebellum, providing a new insight into arsenic neurotoxicity. [Read the Full Post]

Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) exert a strong anti-herpesviral activity

356 | Nov 01 2018

Hutterer C et al. concluded that DYRK signaling represents a promising target pathway for the development of novel anti-herpesviral strategies. [Read the Full Post]

DYRK1B blocks canonical and promotes non-canonical Hedgehog signaling through activation of the mTOR/AKT pathway

343 | Oct 31 2018

Singh R et al. showed that a pharmacological approach combining a DYRK1B antagonist with an mTOR/AKT inhibitor results in strong GLI1 targeting and in pronounced cytotoxicity in human pancreatic and ovarian cancer cells. [Read the Full Post]

Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells

0 | Oct 26 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]

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

0 | Oct 03 2018

Zheng H et al. demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. [Read the Full Post]

CDK1-PDK1-PI3K/Akt signaling pathway regulates embryonic and induced pluripotency

718 | Sep 18 2018

Wang XQ et al. demonstrated an essential role for the CDK1-PDK1-PI3K/Akt kinase signaling pathway in the regulation of self-renewal, differentiation, and somatic reprogramming, which provides a novel kinase cascade mechanism for pluripotency control and acquisition. [Read the Full Post]

P-TEFb Kinase Activity Is Essential for Global Transcription, Resumption of Meiosis and Embryonic Genome Activation in Pig

652 | Sep 18 2018

Oqani RK et al. suggested that P-TEFb kinase activity is crucial for oocyte maturation, embryo development and regulation of RNA transcription in pig. [Read the Full Post]

Triptolide decreases expression of latency-associated nuclear antigen 1 and reduces viral titers in Kaposi's sarcoma-associated and herpesvirus-related primary effusion lymphoma cells

326 | Aug 30 2018

Long C et al. indicated that triptolide impairs the expression of LANA1 and shows antitumor activity against PEL in vitro and in vivo. Triptolide may be a potential agent for treatment of PEL. [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

1822 | 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]

CDK inhibitors suppress Th17 and promote iTreg differentiation, and ameliorate experimental autoimmune encephalomyelitis in mice

406 | Aug 06 2018

Yoshida H et al. suggested that CDK inhibitors modulate TGF-β-signaling pathways, which restore TGF-β-mediated suppression of IL-2 production, thereby modifying the Th17/iTreg balance. [Read the Full Post]

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma

392 | Aug 04 2018

Mersch S et al. described for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies. [Read the Full Post]

Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways

669 | Jul 25 2018

Yang T et al. indicated that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM. [Read the Full Post]

Oxidative stress induces mitotic arrest by inhibiting Aurora A-involved mitotic spindle formation

590 | Jul 24 2018

Wang GF et al. identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases. [Read the Full Post]

Downregulation of the PHLDA1 gene in IMR-32 neuroblastoma cells increases levels of Aurora A, TRKB and affects proteins involved in apoptosis and autophagy pathways

597 | Jul 24 2018

Durbas M et al. showed possible links of the protein to regulation of features of mitochondria and formation of autophagosomes. [Read the Full Post]

Effect of AKT3 expression on MYC- and caspase-8-dependent apoptosis caused by polo-like kinase inhibitors in HCT 116 cells

487 | Jul 18 2018

Nonomiya Y et al. indicated that MYC, caspase-8, P-GP, and AKT3 play critical roles in PLKi-induced apoptosis. Therefore, they are candidate biomarkers of the pharmacological efficacy of PLKis. [Read the Full Post]

Ribonucleotide Reductase Catalytic Subunit M1 (RRM1) as a Novel Therapeutic Target in Multiple Myeloma

431 | Jul 15 2018

Sagawa M et al. demonstrated that RRM1 is a novel therapeutic target in multiple myeloma in the preclinical setting and provide the basis for clinical evaluation of RRM1 inhibitor, alone or in combination with DNA-damaging agents, to improve patient outcome in multiple myeloma. [Read the Full Post]

Genome-wide localization of small molecules

451 | Jul 13 2018

Anders L et al. showed how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. [Read the Full Post]

Transcription of HOTAIR is regulated by RhoC-MRTF-A-SRF signaling pathway in human breast cancer cells

539 | Jul 02 2018

He H et al. suggested that HOTAIR is regulated by the RhoC-MRTF-A-SRF signaling pathway in breast cancer cells. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

2613 | 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]

CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours

0 | Jun 19 2018

Costa-Cabral S et al. suggested that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation. [Read the Full Post]

XL413, a cell division cycle 7 kinase inhibitor enhanced the anti-fibrotic effect of pirfenidone on TGF-β1-stimulated C3H10T1/2 cells via Smad2/4

465 | Jun 06 2018

Jin SF et al. demonstrated that pirfenidone inhibited proliferation, migration and differentiation of TGF-β1-stimulated C3H10T1/2 cells, which could be enhanced by Cdc7 inhibitor XL413, via Smad2/4. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

0 | May 30 2018

Kim HK et al. found that upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

1264 | 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]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

3946 | 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]

Mitotic entry: Non-genetic heterogeneity exposes the requirement for Plk1

553 | May 18 2018

Aspinall CF et al. discussed the implications for developing Plk1 inhibitors as chemotherapy agents and research tools. [Read the Full Post]

Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation Is Required for Apoptotic Activity and Efficient Viral Replication

672 | May 13 2018

Kucharski TJ et al. determined that checkpoint kinase 1 and 2 signaling is important for apoptin regulation and is a likely feature of both tumor cells and host cells producing virus progeny. Inhibition of checkpoint signaling prevents apoptin toxicity in tumor cells and attenuates CAV replication, suggesting it may be a future target for antiviral therapy. [Read the Full Post]

P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest

658 | Apr 18 2018

Shamseddine AA et al. identifyd nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest. [Read the Full Post]

CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours

465 | Apr 17 2018

Costa-Cabral S et al. suggested that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation. [Read the Full Post]

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance

568 | Apr 08 2018

Löschmann N et al. showed that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. Thus, ABCB1 inhibitors may increase the SNS-032 efficacy in ABCB1-expressing cells and prolong or avoid resistance formation. [Read the Full Post]

The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation

907 | Apr 07 2018

Jia L et al. showed that human checkpoint kinase Bub1 not only directly phosphorylates Cdc20, but also scaffolds Plk1-mediated phosphorylation of Cdc20. [Read the Full Post]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

2531 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates

913 | Mar 08 2018

AbdelKhalek A et al. suggested that certain rhodanine compounds may have potential use for the treatment of several multidrug-resistant Gram-positive bacterial infections. [Read the Full Post]

The CDK9 Inhibitor Dinaciclib Exerts Potent Apoptotic and Antitumor Effects in Preclinical Models of MLL-Rearranged Acute Myeloid Leukemia

574 | Mar 06 2018

Baker A et al. highlight a new therapeutic approach to potentially overcome the resistance of MLL-rearranged AML to conventional chemotherapies and prompt further clinical evaluation of CDK inhibitors in AML patients harboring MLL fusion proteins. [Read the Full Post]

Inhibition of Skp2 sensitizes lung cancer cells to paclitaxel

645 | Mar 06 2018

Huang T et al. demonstrated that SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway and that inhibition of Skp2 sensitizes A549 and NCI-H1299 cells to paclitaxel, suggesting that small molecule inhibitors of Skp2 are potential agents for the treatment of lung cancer with upregulation of Skp2. [Read the Full Post]

Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line

952 | Mar 03 2018

Tang ZH et al. showed that EGFR could pose as one of the OSI-resistant mechanisms and navitoclax might be the candidate drug for OSI-resistant NSCLC patients. [Read the Full Post]

Phosphorylation-mediated activation of LDHA promotes cancer cell invasion and tumour metastasis

498 | Feb 26 2018

Jin L et al. demonstrated that LDHA phosphorylation and activation provide pro-invasive, anti-anoikis and pro-metastatic advantages to cancer cells, suggesting that Y10 phosphorylation of LDHA may represent a promising therapeutic target and a prognostic marker for metastatic human cancers. [Read the Full Post]

TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling

446 | Feb 22 2018

Wang B et al. revealed a GβL-ubiquitination-dependent switch that fine-tunes the dynamic organization and activation of the mTORC2 kinase under both physiological and pathological conditions. [Read the Full Post]

Inhibition of mTOR suppresses human gallbladder carcinoma cell proliferation and enhances the cytotoxicity of 5-fluorouracil by downregulating MDR1 expression

0 | Feb 03 2018

Li Q, et al. found 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]

Differentiation of induced pluripotent stem cell-derived neutrophil granulocytes from common marmoset monkey (Callithrix jacchus).

1482 | Jan 27 2018

Schrimpf C et al. indicated cj-iPSC-derived neutrophils bare high hopes in hematologic cell replacement therapy. They exhibit high morphologic similarity to native neutrophils and present neutrophil-specific surface antigens, antimicrobial proteins, and gene products yielding an auspicious approach for continuative experiments including tests in living animals. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

0 | Jan 22 2018

Cayrol F et al. showed that the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [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

482 | Jan 22 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]

Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism

540 | Jan 21 2018

Kuivanen S et al. provided the foundation for development of broad-spectrum cell-directed antivirals or their combinations for treatment of ZIKV and other emerging viral diseases. [Read the Full Post]

Targeting high Aurora kinases expression as an innovative therapy for hepatocellular carcinoma

959 | Jan 16 2018

Liu F et al. provided a solid evidence for SNS-314 as a potential targeted therapy, and a proof-of-concept evidence for a possible combined therapy of SNS-314 plus Hippo pathway inhibitors on HCC. [Read the Full Post]

CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1

513 | Jan 15 2018

Sathe A et al. provided preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription. [Read the Full Post]

Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling

1234 | Jan 04 2018

Dong HM et al. suggested that eHsp90α is a potential therapeutic target for treatment of asthma. [Read the Full Post]

Cathelicidin-WA Improves Intestinal Epithelial Barrier Function and Enhances Host Defense against Enterohemorrhagic Escherichia coli O157:H7 Infection

658 | Dec 31 2017

Yi H et al. showed that CWA attenuated EHEC-induced inflammation, intestinal epithelial barrier damage, and microbiota disruption in the intestine of mice, suggesting that CWA may be an effective therapy for many intestinal diseases. [Read the Full Post]

Organ-specific efficacy of HSP90 inhibitor in multiple-organ metastasis model of chemorefractory small cell lung cancer

703 | Dec 28 2017

Takeuchi S et al. suggested that therapeutic effects of HSP90 inhibitors may be organ-specific and should be carefully monitored in SCLC clinical trials. [Read the Full Post]

Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signaling transduction pathways in high-grade myelodysplastic syndrome

724 | Dec 12 2017

Xu F et al. indicated that rigosertib is a selective and promising anti-tumor agent that could ameliorate multiple dysregulated signaling transduction pathways in high-grade MDS. [Read the Full Post]

Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

1012 | Dec 11 2017

Maimaiti Y, et al. indicated that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer. [Read the Full Post]

The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy

867 | Dec 11 2017

Zhou ZR et al. suggested that MK-8776 increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC. [Read the Full Post]

Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells

593 | Dec 05 2017

Xie S et al. showed that CDK inhibitor LS-007 potently inhibits the established human AL cell lines and primary AL blasts, and it also shows remarkable synergy with Bcl-2 inhibitor ABT-199. [Read the Full Post]

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance

804 | Nov 19 2017

demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. Thus targeting DNA replication and G2-M cell cycle checkpoint simultaneously by cisplatin and WEE1 inhibition is promising for TNBCs treatment, and for overcoming their cisplatin resistance. [Read the Full Post]

Molecular mechanism of G1 arrest and cellular senescence induced by LEE011, a novel CDK4/CDK6 inhibitor, in leukemia cells

651 | Nov 08 2017

Tao YF et al. demonstrated for the first time that LEE011 treatment results in inhibition of cell proliferation and induction of G1 arrest and cellular senescence in leukemia cells. LncRNA microarray analysis showed differentially expressed mRNAs and lncRNAs in LEE011-treated HL-60 cells and we demonstrated that LEE011 induces cellular senescence partially through downregulation of the expression of MYBL2. These results may open new lines of investigation regarding the molecular mechanism of LEE011 induced cellular senescence. [Read the Full Post]

Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors

753 | Nov 07 2017

Zhang M et al. identified AJUBA, SMAD4 and RAS mutations as potential candidate biomarkers of response of HNSCC to treatment with these mitotic inhibitors. [Read the Full Post]

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

0 | Nov 06 2017

Isono M et al. showed that AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy. [Read the Full Post]

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

901 | Nov 02 2017

Rasmussen RD et al. proposed that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

0 | Oct 29 2017

Noguchi K et al. suggested that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells

728 | Oct 26 2017

Bista R et al. provided evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL. [Read the Full Post]

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype

971 | Oct 14 2017

Schultz MJ et al. found that ST6Gal-I induced expression of the key tumor-promoting transcription factors, Sox9 and Slug [Read the Full Post]

Expression and clinical significance of Wee1 in colorectal cancer

0 | Oct 12 2017

Egeland EV et al. indicated that other tumor types might be better suited for further development of Wee1 inhibitors. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

0 | Oct 11 2017

Chang X et al. reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

0 | Oct 06 2017

Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

1461 | Oct 04 2017

Song Z et al. suggested that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [Read the Full Post]

PARP inhibitor increases chemosensitivity by upregulating miR-664b-5p in BRCA1-mutated triple-negative breast cancer

709 | Oct 02 2017

Song W et al. showed that miR-664b-5p functions as a tumour suppressor and has an important role in the regulation of PARP inhibitors to increase chemosensitivity by targeting CCNE2. This may be one of the possible mechanisms by which PARP inhibitors increase chemosensitivity in BRCA1-mutated TNBC. [Read the Full Post]

In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

0 | Sep 27 2017

Perez-Peña J et al. demonstrated the antitumor effect of this new family of compounds in TNBC, paving the way for its future clinical development. [Read the Full Post]

The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway

855 | Sep 15 2017

Wang C et al. indicate that the Rac1 protein may be the key target involved in the radiosensitization of nasopharyngeal carcinoma cells. [Read the Full Post]

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

1841 | Sep 09 2017

Thompson JM et al. suggested that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma

878 | Aug 22 2017

Gutteridge RE et al. suggested that PLK1 may be an important regulator of metabolism maintenance in melanoma cells. [Read the Full Post]

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

1647 | Aug 20 2017

Isono M et al. showed that AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy. [Read the Full Post]

Plasmonic nanocarrier grid-enhanced Raman sensor for studies of anticancer drug delivery

1143 | Aug 20 2017

Kurzątkowska K et al. demonstrated that the proposed nanocarrier SERS sensor can be utilized to investigate attachment of targeting ligands to nanocarriers (attachment of folic acid ligand recognized by folate receptors of cancer cells is described). Further testing of the nanocarrier SERS sensor involved drug release induced by lowering pH and increasing GSH levels, both occurring in cancer cells. The proposed sensor can be utilized for a variety of drugs and targeting ligands, including those which are Raman inactive, since the linkers can act as the Raman markers, as illustrated with mercaptobenzoic acid and para-aminothiophenol. [Read the Full Post]

Nuclear PTEN interferes with binding of Ku70 at double-strand breaks through post-translational poly(ADP-ribosyl)ation

836 | Aug 14 2017

Guan J, et al. provided contributes to understanding the effect of PTEN in repair of DSB and using defined anti-tumor DSB drugs to treat tumor cells with aberrant PTEN. [Read the Full Post]

HOXC10 Expression Supports the Development of Chemotherapy Resistance by Fine Tuning DNA Repair in Breast Cancer Cells

0 | Aug 04 2017

Sadik H et al. showed that HOXC10 facilitates, but is not directly involved in DNA damage repair mediated by HR. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

1373 | Jul 31 2017

Noguchi K et al. suggests that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells

1223 | Jul 30 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]

Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors

963 | Jul 23 2017

Zhang M et al. identified AJUBA, SMAD4 and RAS mutations as potential candidate biomarkers of response of HNSCC to treatment with these mitotic inhibitors. [Read the Full Post]

Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells

0 | Jul 19 2017

Wu X et al. demonstrated that GP130/STAT3 signaling contributes to the resistance of these drugs in rhabdomyosarcoma cells. They also suggested a potentially novel cancer therapeutic strategy using the combination of inhibitors of GP130/STAT3 signaling with doxorubicin, cisplatin, or AZD6244 for rhabdomyosarcoma treatments. [Read the Full Post]

MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers

1750 | Jul 18 2017

Zhou J et al. concluded that miR-193a-5p induced cisplatin resistance by repressing AP-2α expression in bladder cancer cells. [Read the Full Post]

The RNA-Binding Proteins Zfp36l1 and Zfp36l2 Enforce the Thymic β-Selection Checkpoint by Limiting DNA Damage Response Signaling and Cell Cycle Progression

1901 | Jul 16 2017

Vogel KU et al. showed that in addition to controlling the timing of proliferation at β-selection, posttranscriptional control by Zfp36l1/l2 limits DNA damage responses, which are known to promote thymocyte differentiation. Zfp36l1/l2 therefore act as posttranscriptional safeguards against chromosomal instability and replication stress by integrating pre-TCR and IL-7 signaling with DNA damage and cell cycle control. [Read the Full Post]

METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion

1557 | Jul 16 2017

Zhang Z et al. identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. [Read the Full Post]

Identification of DYRK1B as a substrate of ERK1/2 and characterisation of the kinase activity of DYRK1B mutants from cancer and metabolic syndrome

893 | Jul 13 2017

Ashford AL et al. showed that DYRK1B is a novel ERK2 substrate, uncovering new links between two kinases involved in cell fate decisions. Finally, we show that DYRK1B mutants that have recently been described in cancer and metabolic syndrome exhibit normal or reduced intrinsic kinase activity. [Read the Full Post]

Ras oncogene-independent activation of RALB signaling is a targetable mechanism of escape from NRAS(V12) oncogene addiction in acute myeloid leukemia

999 | Jul 09 2017

Pomeroy EJ et al. demonstrated that Ras oncogene-independent activation of RALB signaling is a therapeutically targetable mechanism of escape from NRAS oncogene addiction in AML. [Read the Full Post]

A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer

1219 | Jul 09 2017

Lin SF et al. findings support dinaciclib as a potential drug for further studies in clinical trials for the treatment of patients with refractory thyroid cancer. [Read the Full Post]

Phosphorylation of Astrin Regulates Its Kinetochore Function

0 | Jul 01 2017

Chung HJ et al. revealed a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome [Read the Full Post]

Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth

1447 | Jun 28 2017

Parra K et al. proved Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

3566 | Jun 18 2017

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer

1026 | Jun 18 2017

Lok BH et al. found that SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC and we identify combinatorial therapy with TMZ as a particularly promising therapeutic strategy that warrants further clinical investigation. [Read the Full Post]

Cyclin D1 depletion induces DNA damage in mantle cell lymphoma lines

960 | Jun 09 2017

Mohanty S et al. had an important implication for CCND1 as a potential therapeutic target in MCL patients who are refractory to standard chemotherapy. [Read the Full Post]

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

2749 | Jun 06 2017

Guo SC et al. provided evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. [Read the Full Post]

The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line

1673 | Jun 02 2017

Wang J et al. found that serine/threonine AK inhibition, essentially with VX-680, could be a promising, specific therapeutic tool for eradicating metastases in adrenocortical tissue. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

0 | May 22 2017

Massa MG et al. provided an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

0 | May 12 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Function of AURKA protein kinase in the formation of vasculogenic mimicry in triple-negative breast cancer stem cells

2929 | Apr 30 2017

Liu Y et al. suggested that AURKA protein kinase is involved in VM formation of CSCs and may become a new treatment target in suppressing VM and metastasis of breast cancer. [Read the Full Post]

Enhancing glioblastoma cell sensitivity to chemotherapeutics: a strategy involving survivin gene silencing mediated by gemini surfactant-based complexes

0 | Apr 26 2017

Cruz RQ et al showed that survivin downregulation combined with administration of the chemotherapeutic agents temozolomide or etoposide resulted in a synergistic cytotoxic effect, thus revealing to be a promising strategy to reduce the chemotherapeutic doses for GBM treatment. [Read the Full Post]

Electrochemical biosensor for protein kinase A activity assay based on gold nanoparticles-carbon nanospheres, phos-tag-biotin and β-galactosidase

2540 | Apr 21 2017

Zhou Y et al. found the fabricated biosensor can be applied to detect PKA in human normal gastricepithelial cell line and human gastric carcinoma cell line with satisfactory results. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

2243 | Apr 18 2017

Yi H et al found weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

0 | Apr 06 2017

Hsu YC et al showed that activation of AurA kinase through FGF1/FGFR signaling axis sustains the stem cell characteristics of GBM cells. [Read the Full Post]

Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer

969 | Mar 23 2017

Chen J et al. suggested that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Mar 13 2017

Sampson VB et al suggested that potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Activation of Fibroblast-like Synoviocytes in Regulates Migration, Invasion, and Protein Inhibitor of Activated STAT3 Rheumatoid Arthritis

1084 | Mar 01 2017

Lao M, et al.'s observations suggest that PIAS3 suppression may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, and activation. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

0 | Feb 28 2017

Ma HT, et al.'s results provide a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeuticmediated cell death

1538 | Feb 27 2017

Chen H, et al.'s results establish the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1

946 | Feb 26 2017

Sathe A, et al. provide preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription. [Read the Full Post]

Epithelial-Mesenchymal Transition Predicts Polo-Like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer

1295 | Feb 13 2017

In Ferrarotto R, et al.'s first reported large-scale integrated analysis of PLK1 inhibitor sensitivity, we demonstrated that EMT leads to PLK1 inhibition sensitivity of NSCLC cells. Our findings have important clinical implications for mesenchymal NSCLC, a significant subtype of the disease that is associated with resistance to currently approved targeted therapies. [Read the Full Post]

RNA polymerase I transcription is modulated by spatial learning in different brain regions.

1108 | Feb 08 2017

Capitano F, et al.'s results suggest that de novo rRNA transcription is a necessary step for spatial memory consolidation and that after learning it occurs in several brain regions with a complex spatio-temporal dynamic. This article is protected by copyright. All rights reserved. [Read the Full Post]

Vorinostat Enhances Cytotoxicity of SN-38 and Temozolomide in Ewing Sarcoma Cells and Activates STAT3/AKT/MAPK Pathways

0 | Jan 21 2017

In Sampson VB, et al.'s summary, potent antiproliferative and proapoptotic activity were demonstrated for ST induced DNA damage before or simultaneous with HDAC inhibition and cell death was mediated through the p53 pathway. These observations may aid in designing new protocols for treating pediatric patients with high-risk EWS. [Read the Full Post]

Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing antimitotic therapeutic-mediated cell death

1693 | Jan 15 2017

Chen H et al. found the importance of SIK3 as a mitotic regulator and underscore the potential of SIK3 as a druggable antimitotic target. [Read the Full Post]

Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15-dependent drug resistance

1748 | Jan 15 2017

Ma HT et al. provided a molecular basis for increasing the effectiveness of Aurora A and KIF11 inhibitors and tackling problems of drug resistance. [Read the Full Post]

CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1

0 | Jan 13 2017

Sathe A, et al. provide preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription. [Read the Full Post]

Epithelial-Mesenchymal Transition Predicts Polo-Like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer

1224 | Jan 06 2017

The study of Ferrarotto R, et al. demonstrated that EMT leads to PLK1 inhibition sensitivity of NSCLC cells. Our findings have important clinical implications for mesenchymal NSCLC, a significant subtype of the disease that is associated with resistance to currently approved targeted therapies. [Read the Full Post]

RNA polymerase I transcription is modulated by spatial learning in different brain regions.

0 | Jan 03 2017

J Neurochem's results suggested that de novo rRNA transcription is a necessary step for spatial memory consolidation and that after learning it occurs in several brain regions with a complex spatio-temporal dynamic. [Read the Full Post]

Phosphorylation of Astrin Regulates Its Kinetochore Function

0 | Dec 26 2016

Chung HJ et al. revealed a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome integrity. [Read the Full Post]

Phosphorylation of Astrin Regulates Its Kinetochore Function

1216 | Dec 23 2016

Chung HJ et al. revealed a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome integrity. [Read the Full Post]

HOXC10 Expression Supports the Development of Chemotherapy Resistance by Fine Tuning DNA Repair in Breast Cancer Cells

1193 | Dec 11 2016

Sadik H et al. found that inhibitors of CDK7 reverse HOXC10-mediated drug resistance in cultured cells. Blocking HOXC10 function, therefore, presents a promising new strategy to overcome chemotherapy resistance in breast cancer. [Read the Full Post]

The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway

0 | Dec 01 2016

Wang C, et al. found that the activated Rac1/NADPH pathway combined with radiation can increase the radiosensitivity of nasopharyngeal carcinoma cells, and the Rac1/NADPH pathway may be the signaling pathway involved in the radiosensitization process. [Read the Full Post]

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

1851 | Nov 23 2016

Hain KO et al. demonstrated that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis. [Read the Full Post]

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

1784 | Nov 17 2016

Chang X et al. revealed that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. [Read the Full Post]

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer

1758 | Nov 17 2016

Ju HQ et al. revealed a novel regulatory mechanism for Nampt in PDAC and suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. [Read the Full Post]

Expression and clinical significance of Wee1 in colorectal cancer

1515 | Nov 16 2016

The lack of clinical significance of Wee1 expression could indicate that other tumor types might be better suited for further development of Wee1 inhibitors. [Read the Full Post]

The Tumor-Associated Glycosyltransferase ST6Gal-I Regulates Stem Cell Transcription Factors and Confers a Cancer Stem Cell Phenotype

1635 | Nov 13 2016

Schultz MJ et al. highlighted a previously unrecognized role for a specific glycosyltransferase in driving a CSC state. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

3809 | Oct 19 2016

[Read the Full Post]

Activation of Aurora A kinase through the FGF1/FGFR signaling axis sustains the stem cell characteristics of glioblastoma cells

1995 | Sep 09 2016

Hsu YC et al. identified a novel mechanism for the malignancy of GBM, which could be a potential therapeutic target for GBM. [Read the Full Post]

Protein Inhibitor of Activated STAT3 Regulates Migration, Invasion, and Activation of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

1346 | Sep 01 2016

Lao M, et al. suggested that PIAS3 suppression may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, and activation. [Read the Full Post]

The role of nuclease FAN1 in DNA crosslink repair in Arabidopsis thaliana

2459 | Mar 26 2015

Herrmann et al. demonstrated that FAN1 homolog is present in plants and is proved to be involved in Arabidopsis thaliana CL repair. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

8745 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

9468 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

Recently identified CHEK2 Y390C mutation facilitates early breast cancer development

6183 | Feb 05 2015

Wang et al. identified a missense variant Y390C of CHEK2 that related to tumorigenesis in high-risk breast cancer patients. [Read the Full Post]

A protocol for human pluripotent stem cell differentiation into endoderm related cells

6844 | Feb 02 2015

Diekmann et al. showed a detailed protocol started from a defined cell number of dispersed single cells of three different human ESC lines, and one human iPSC line. [Read the Full Post]

The distribution of primary cilia in the mouse embyo

4563 | Jan 27 2015

Bangs et al. demonstrate the time and location that primary cilia appear in the mouse embryo. [Read the Full Post]

Cep68 act as an important linker protein of centrosomes and centriole disengagement

4565 | Dec 26 2014

Pagan et al. indentified the important roles of Cep68 and other related factors during the disengagement of centrosomes and entrioles. [Read the Full Post]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

7992 | Dec 04 2014

Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. [Read the Full Post]

Quickly switching of spindle checkpoint states is due to negative feedback at kinetochrores

4096 | Nov 27 2014

Nijenhuis et al. found this phenomenon arises due to localized negative feedback of spindle assemble checkpoint (SAC) signal, which ensure kinetochres switch SAC signalling OFF rapidly. [Read the Full Post]

ERK/Cdk5 axis regulates diabetes-related PPARγ phosphorylation

7278 | Nov 21 2014

Recently, Banks et al. discovered that ERK/Cdk5 axis is involved in regulation PPARγ activities, and the inhibition of ERK and MEK leads to the improvement of insulin resistance. [Read the Full Post]

Is it really that nonselective inhibitors have no future in clinical study

2269 | Apr 01 2014

R547 is a potent ATP-competitive inhibitor of CDK1/2/4 with Ki of 2 nM/3 nM/1 nM. It is less potent to CDK7 and GSK3α/β, while inactive to other kinases. [Read the Full Post]

Y27632 is a biochemical tool used in the study of the ROCK

5319 | Mar 05 2014

Y-27632 2HCl inhibits ROCK-II while displaying little activity against PKC. [Read the Full Post]

Here we assess the in vitro and in vivo anti MM activity of MLN8237

2498 | Feb 26 2014

MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. [Read the Full Post]

Roscovitine is an experimental drug in the family

2123 | Feb 25 2014

Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. [Read the Full Post]

Adriamycin is an anti cancer chemotherapy drug

0 | Jan 27 2014

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

Y 27632 is available in a 5 mg format and has been optimized

5050 | Jan 17 2014

Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

R547 is a potent and selective ATP competitive CDK inhibitor

2235 | Jan 16 2014

R547 is a potent ATP-competitive inhibitor of CDK1/2/4 with Ki of 2 nM/3 nM/1 nM. It is less potent to CDK7 and GSK3α/β, while inactive to other kinases. [Read the Full Post]

Adriamycin is photosensitive and containers

2558 | Jan 10 2014

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

Y 27632 is a biochemical tool used in the study of the rho associated protein kinase

5139 | Jan 10 2014

Y-27632 2HCl is a selective ROCK1 inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

Roscovitine is an experimental drug candidate in the family

2389 | Jan 07 2014

Roscovitine is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. [Read the Full Post]

NU7441 is a potent novel DNA PK inhibitor

2513 | Dec 26 2013

NU7441 is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits PI3K with IC50 of 5 μM. [Read the Full Post]

R547 is a potent ATP competitive inhibitor of CDK

2411 | Dec 10 2013

R547 identified as a diaminopyrimidine compound, which is a potent and selective ATP-competitive CDK inhibitor. [Read the Full Post]

Adriamycin is an anti cancer chemotherapy drug

2802 | Dec 02 2013

Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis. [Read the Full Post]

Decitabine is a drug for the treatment of myelodysplastic syndromes

2691 | Nov 22 2013

Decitabine is a potent inhibitor of DNA methylation with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively. [Read the Full Post]

Thiazovivin helps in promoting human embryonic stem cell

4916 | Nov 22 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

Roscovitine is a cell permeable reversible selective inhibitor

2484 | Nov 21 2013

Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. It shows little effect on CDK4/6. [Read the Full Post]

Roscovitine is an experimental drug candidate in the family of pharmacological

2669 | Nov 19 2013

Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM. It shows little effect on CDK4/6. [Read the Full Post]

Thiazovivin is a drug which dramatically improves the survival of hES

5204 | Nov 05 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

MK 8776 is a potent and functionally selective targeting cell

2628 | Oct 30 2013

SCH 900776 is not a potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. [Read the Full Post]

PHA848125 is a spectrum selective multi kinase inhibitor of cyclin dependent kinases

2357 | Sep 17 2013

PHA-848125 is a potent, ATP-competitive CDK inhibitor for CDK2 with IC50 of 45 nM. It is >3-fold more selective for CDK2 than CDK1, 2, 4, 5, and 7. Phase 2. [Read the Full Post]

Y27632 is a selective inhibitor of the Rhoassociated kinase p160ROCK

4981 | Sep 12 2013

Y27632 2HCl inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with Ki of 26 μM, 25 μM and > 250 μM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. [Read the Full Post]

STA9090 is a novel synthetic small molecule inhibitor of heat shock protein 90

2341 | Aug 31 2013

Ganetespib is an HSP90 inhibitor with IC50 of 4 nM in OSA 8 cells, induces apoptosis of OSA cells while normal osteoblasts are not affected; active metabolite of STA-1474. [Read the Full Post]

Roscovitine is an experimental drug candidate

2642 | Aug 12 2013

Saracatinib also potently inhibits other Src tyrosine kinase family members including c-Yes, Fyn, Lyn, Blk, Fgr, and Lck with IC50 from 4-10 nM. Saracatinib sensitively inhibits Src Y530F NIH 3T3 with IC50 of 80 nM. [Read the Full Post]

PHA767491 is a newly discovered type of antitumor drugs

2383 | Jul 23 2013

PHA-767491 displays approximately 20-fold selectivity for Cdk1, Cdk2 and GSK3-β, 50-fold selectivity for MK2 and Cdk5 and 100-fold selectivity for PLK1 and CHK2. [Read the Full Post]

SCH 900776 is targeting cell cycle checkpoint kinase

3016 | Jun 08 2013

SCH 900776 is not a potent inhibitor of Chk2 and CDK2 with IC50 of 1.5 μM and 0.16 μM, respectively. SCH 900776 shows no significant inhibition of cytochrome P450 human liver microsomal isoforms 1A2, 2C9, 2C19, 2D6, and 3A4. [Read the Full Post]

y27632 is a biochemical tool used in the study of the rho associated protein kinase signaling pathways

5449 | Jun 07 2013

Oral administration of Y-27632 2HCl at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. [Read the Full Post]

Olaparib for the treatment of the BRCA1 or BRCA2 gene mutations in cancer

3178 | Jan 23 2013

A broad range of pathological disorders is linked to oxidative stress, including carcinogenesis and several age-dependent disorders . Oxidative stress is defined as an imbalance Olaparib in which the production of reactive oxygen species overcomes the antioxidative cell defence system [Read the Full Post]

Alvocidib is a cyclin dependent kinase inhibitor under clinical development for the treatment

1620 | Jan 17 2013

Alvocidib is also considered a major pathogenic factor. Lipid A, also referred to as endotoxin, is the hydrophobic membrane anchor of LPS and is known to be a potent inducer of the host innate immune system [Read the Full Post]

ROCK Kinase is involved in cytokinesis

5380 | Dec 03 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the contribution of the JNK pathway in the regulation of smooth muscle contraction. crosstalk between MAPK and JNK by other means NFkB not well ROCK Kinase understood. [Read the Full Post]

Dinaciclib is supported by several previous studies

2313 | Nov 30 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the Dinaciclib contribution of the JNK pathway in the regulation of smooth muscle contraction [Read the Full Post]

CANCER AND CDK INHIBITION

3148 | Sep 16 2012

CDK/CYCLIN DEPENDENT KINASES: Among a large number of cell cycle regulators, cyclin dependent kinases also known as CDKs are known to be very important ones. These kinases play a crucial role in the processes of transcription, mRNA processing and cellular differentiation. These kinases have a small structure with an important kinase domain and depend on another small protein for proper activity i.e., cyclin. As these are very important kinases in cell cycle, they can be targeted in order to prevent proliferation of cancer cells. Inhibition of these kinases has shown induction of apoptosis especially in cancer cells. Various inhibitors have been designed against different kinases to fight cancer and inflammation, preserved in kinase inhibitor library for screening amongst these CDK2 inhibitors have been found to be most effective. Inhibiting cell cycle regulators may have some hazards as well; therefore inhibitors should be developed carefully in order to avoid these side effects. [Read the Full Post]

CANCER INHIBITION BY CDK

3020 | Aug 09 2012

CYCLIN DEPENDENT KINASES OR CDK: Cyclin dependent kinases or CDKs are also found to be very famous ones among the long list of regulators of cell cycle. These kinase enzymes play a very crucial role in various processes like mRNA processing, cellular differentiation and, transcription. These kinase enzymes have a very important kinase domain and a small structure and they also depend upon another protein i.e cyclin for their proper activity. To stop the proliferation of cancer or tumor cells these kinases can be targeted as they are an important part of cell cycle. By the inhibition of these kinase enzymes apoptosis is induced in the cells especially the tumor cells. Different kinase inhibitors have been designed to fight against these kinases and stop the inflammation, conserved in the kinase inhibitor library and amongst these inhibitors, CDK inhibitors were found to be very effective ones. The inhibition of the regulators of cell cycle may also cause some hazards; so the inhibitors should be designed very carefully and efficiently in order to avoid the side effects. [Read the Full Post]

CDK INHIBITOR AND CELL CYCLE

2823 | Jul 27 2012

CYCLIN DEPENDENT KINASES OR CDKs: Cyclin dependent kinases are amongst one of the most vital kinase enzymes in the regulation of cell cycle. These are also abbreviated as CDKs and due to a crucial role these enzymes are implicated in transcription, nerve cells differentiation, and mRNA processing. These enzymes have small structure but having an important part that is kinase domain. It is reported that the inhibition of CDK leads to the apoptosis of cells specifically in case of cancer cells, so it is important in controlling the cell cycle. Uncontrolled cellular proliferation can lead to the cell cycle aberrations. Various compounds found in kinase inhibitor library have shown activity against inflammations and cancer and among these inhibitors CDK inhibitors are most effective against CDKs. The development of inhibitors has to be performed carefully as there may be some of the other potential hazards of cell cycle dysregulation and some other effects as well. [Read the Full Post]

CDK INHIBITORS IN REGULATING CELL CYCLE

2373 | Mar 20 2012

Introduction: Cyclin dependent Kinases In total 512 human versions serine/therione/tyrosine kinases have been discovered leading to the theoretical formation of multiple pathways that govern all aspects of cellular life and death. Research has confirmed many of these controls but aspects of these mechanisms still remain controversial. One of earliest kinase pathways to be discovered was the Cyclin dependant kinases. These kinases were shown to be a major regulatory mechanism of the cell cycle growth patterns, apoptotic processes, pain, gene transcription, and RNA formation. Mechanisms with which CDK action and response is controlled can be by phosphorylation or degradation, natural inhibitory proteins, movement of the kinase around the cell or nucleus and by formation complexes with other regulatory proteins. [Read the Full Post]

ROSCOVITINE – A CONTROLLER OF THE CYCLINS

1763 | Mar 20 2012

CDKs AND CANCER: In cellular regulation which is one of the important processes, different enzymes are important and among these cyclin dependent kinases or CDKs play vital role. Mostly cancers are linked with malfunctioning of these CDKs. There are two forms of these malfunctioning, one is the over expression of the CDKs gene and second is about the regulatory proteins of CDKs which may be absent or abnormal. In the field of cancer treatment various inhibitor have been developed which inhibit the function of different vital enzymes. In case of CDKs the development of the unique compound to inhibit the activity of abnormal enzymatic activity is not as simple because the activity of different CDKs is time specific in the cell cycle, therefore a molecule should be well timed up with CDKs. A good number of CDK inhibitors are developed and are mostly in clinical trials phases among those Roscovitine CDK inhibitor is active inhibitor. [Read the Full Post]

THIAZOVIVIN: THE PLURIPOTENCY INDUCER

4306 | Mar 20 2012

POTENTIAL OF EMBRYONIC STEM CELLS OF HUMAN (hESCs): The stem cells are not only known for their property of pluripotency in nature which means they have the potency to replicate in an indefinite manner but also famous for their capability of getting differentiate into all other kinds of cells and organelles from the three basic germinal layers named as ectoderm, mesoderm and endoderm. Embryonic stem cells of human (hESCs) have the ability of producing various numbers of types of cells in contrast to adult stem cells having the capability of producing only a limited cell types. Due to their pluripotency hESCs or human embryonic stem cells are of great interest and importance for the scientists and researchers as they are being used for detection and analysis of different genetic disorders of human in their research. The successful models of Human Embryonic Stem Cells are made for Fragile-X syndrome and Cystic fibrosis (CF) etc like genetic maladies and their will be many more in upcoming years. In olden years the usual practice was to use embryo to generate pluripotent stem cells which is brought down very significantly due to the process of insertion of various genes like Sox2, Oct4 and Klf4 etc into differentiated cells. These genes can enhance the pluripotency in differentiated cells and make them exactly like embryonic stem cells. A recent more advanced approach is to use molecules like Thiazovivin. [Read the Full Post]

CDK INHIBITOR AGAINST CELL CYCLE DYSREGULATION

1930 | Mar 19 2012

The cell Cycle One of the most important discoveries of the 20th century was the revelations of how cells were governed and regulated in their growth patterns. This process was described in a cell cycle pathway along with regulatory mechanism and quality control functions. Each individual cell is capable of replicating itself but is not always in the processes of doing so. This resting state is referred to as the G0 phase. An extracellular signal is sent to the cell via the cell surface receptors that trigger the cell to enter the G1 phase. This is the first step in cell replication and the cell gathers nutrients as well as protein building blocks from the systemic circulation, this allows the cell to increases in size. Control proteins regulate the amount of material gathered by the cell and the size to which in grows. If certain specifications are met the cell moves from the G1 phase to the S phase of the process. [Read the Full Post]

PD 0332991 – THE POTENT CDK INHIBITOR

2985 | Mar 19 2012

PD 0332991 PROPERTIES: One of the most important functions any cell can do is the reproduction of itself, identical down to the finest degree. The process that achieves the basic necessity of life itself is called the cell cycle and is a highly controlled / regulated process. This process is divided into two stages; the first is the interphase stage which has four distinct phases. The second stage is the cell division stage and this consists solely of the cell mitosis. Starting at stage 1 the cell is usually at rest or in a condition where no replication is occurring, this is referred to as the G0 phase. When a cell receives an external trigger to divide the cell moves into the G1 phase, here the cell will accumulated nutrients and molecules necessary for the construction of all the components of a new cell. Cells use this material to increase in size to accommodate the new material and to generate sufficient cell membrane so a division can occur. The G1 phase has control mechanisms to recognize the successful completion of all necessary components of this phase. [Read the Full Post]

AZD1152 – AN AURORA KINASE INHIBITOR

5436 | Mar 13 2012

Inhibition of AURORA KINASES in relation to cancer: Mitosis is a key process in the regeneration of cellular material and two key regulators of this function are serine and threonine kinases which are more commonly known as Aurora Kinases. Three isoforms of the aurora kinase have been isolated in human tissue (A,B and C) which function on different aspects of the mitosis cycle. Aurora kinases are significant as targets for chemotherapeutic action since they are elevated in many different cancer types. Small molecule inhibitors of aurora kinases, such as VX-680 (Tozasertib), ZM447439 and Hesperadin, have been developed and successfully trialed on several cancer groups including breast, colon, prostate and in acute myeloid leukemia (AML). [Read the Full Post]

ROSCOVITINE – CONTROLLING THE CYCLINS

2864 | Mar 13 2012

Introduction: Cyclin-dependant kinase Inhibitors: Another family of proteins that are involved in the regulation of cellular growth are the cyclin dependant kinases (CDK’s). These enzymes are known to be involved in the regulation of the cell cycle (Mitosis (M phase) – Gap phase (G1) – Synthesis (S) – Gap phase (G2)) as well as regulating transcription, mRNA and differentiation of nerve cells. CDK’s contain not much more than a kinase domain and are serine / threonine phosphorylators. The substrate for CDK’s is a regulatory protein called cyclin of which 12 are known. The activity of CDK’s is restricted to the CDK – complex which in human cells there are at least 9 known variations. Different CDK-complexes are involved at different stages of the cell cycle process each one controlling one or more factors. In current theory CDK’s are the diving motivation behind each phase of the cell cycle and deviations in the CDK activity from the normal can cause unregulated proliferation or simple a tumor. Hence direct targeting of the aberrant CDK activity would ideally be a therapeutic possibility. However, with CDK activity essential for all cell cycle processes there was no theoretical distinction between tumor and normal cells hence significant toxicology could be expected. Recently new research changed this theory; it indicated that tumor cell cycle was controlled by an interphase CDK that was specific to the tumor cell. With this inhibitors of CDK activity could now be implemented against tumor growth patterns. For this purpose smaal molecule inhibitors were designed, of which the Roscovitine CDK inhibitor is one of several being tested in certain tumor types. [Read the Full Post]

TOZASERTIB IN CLINICS FOR AURORA INHIBITION

5080 | Mar 13 2012

AURORA KINASE INHIBITION AND TOZASERTIB:  Three isoforms of the aurora kinase have been isolated in human tissue (A,B and C) which function on different aspects of the mitosis cycle. Aurora kinases are significant as targets for chemotherapeutic action since they are elevated in many different cancer types. Small molecule inhibitors of aurora kinases, such as VX-680 (Tozasertib), ZM447439 and Hesperadin have been developed and successfully trialed on several cancer groups including breast, colon, prostate and in acute myeloid leukemia (AML). The initial results obtained for the Tozasertib Aurora kinase inhibitor has lead to its advancement into phase 1 and phase 2 clinical trials. [Read the Full Post]

The combination of VE-465 and vincristine, the potential therapy for leukemia

7123 | Oct 25 2011

Leukemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of white blood cells, and studies on the treatment of the disease have been carried out for many years. At present, a variety of small-molecule agents targeting specific leukemogenetic molecules have been used in preclinical or clinical treatment of leukemia. For example, BCR/ABL kinase inhibitors, including imatinib, nilotinib and dasatinib have shown the effective treatment against BCR/ABL-positive leukemia. However, novel agents and therapy may be still needed, since monotherapy shows only limited clinical efficacy. [Read the Full Post]

Novel CDK2 Inhibitors as Anti-Tumor Agents

2514 | Sep 09 2011

Conventional anti-cancer drugs have mainly focused on targeting DNA synthesis and cell division.n order to avoid these adverse effects, investigators begin to develop a new class of anti-cancer agents, and signal transduction or secondary message inhibitors is one of the successful research findings. [Read the Full Post]

Takayuki Ikezoe (2008). “Aurora kinases as an anti-cancer target” Cancer Letters 262(2-3): 1–9

4218 | Jun 13 2011

This review highlights the function of Aurora kinases in the regulation of mitosis and presents the rationale for these kinases as an anti-cancer target. I also review recently developed inhibitors of Aurora kinases. [Read the Full Post]

Narumiya, S., M. Tanji, et al. (2009). "Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion." Cancer Metastasis Rev 28(1-2): 65-76.

5148 | Jun 7 2011

This review summaries the Rho signaling in transformation, metastasis and invasion. It explains the relationship between Rho signaling and tumor cells, and it gives the perspectives in this review. [Read the Full Post]

Peters, J. M. (2006). "The anaphase promoting complex/cyclosome: a machine designed to destroy." Nat Rev Mol Cell Biol 7(9): 644-656.

3405 | May 8 2011

This article which was published in Nature review molecular cell biology reviews not only APC/C subunits and substrates, but the functions, regulation, and inhibition of APC during the 10 years since APC was discovered. [Read the Full Post]

Barr, F. A., H. H. Sillje, et al. (2004). "Polo-like kinases and the orchestration of cell division." Nat Rev Mol Cell Biol 5(6): 429-440

3189 | Apr 22 2011

This review introduces the Plk structure and regulation, Plk function at the G2/M transition, in cytokinesis, and chromosome segregation, and the interaction between PLKs and other targets. [Read the Full Post]

Riento, K. and A. J. Ridley (2003). "Rocks: multifunctional kinases in cell behaviour." Nat Rev Mol Cell Biol 4(6): 446-456.

4468 | Mar 3 2011

This article introduces regulation of ROCK activity, ROCK function and ROCK inhibitors. This review concludes knowledge of ROCK in different ways. [Read the Full Post]