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Cell Cycle

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

16 | 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

42 | 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

29 | 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

32 | 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

30 | 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

23 | 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

28 | 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

67 | 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

57 | 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

40 | 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]

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

120 | 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

68 | 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)

68 | 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]

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

58 | 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]

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

58 | 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

59 | 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

86 | 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

86 | 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]

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

71 | 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

76 | 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]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

201 | 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

188 | 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]

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

60 | 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

90 | 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]

Inhibition of Suicidal Erythrocyte Death by Volasertib

104 | 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

127 | 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]

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

109 | 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

103 | 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

110 | 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]

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

190 | 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

207 | 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

259 | 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

139 | 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

144 | 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

156 | 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

550 | 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

174 | 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

216 | 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

183 | 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

482 | 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

432 | 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]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

1243 | 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

290 | 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]

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

471 | 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

428 | 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

420 | 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

346 | 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]

Genome-wide localization of small molecules

315 | 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

402 | 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

1941 | 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

321 | 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

948 | 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

2916 | 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

407 | 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

481 | 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

502 | 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

324 | 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

434 | 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

772 | 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

1945 | 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]

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

438 | 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

512 | 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]

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

1225 | 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

392 | 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

405 | 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

781 | 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

403 | 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

995 | 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

504 | 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

550 | 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

592 | 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

806 | 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

721 | 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

490 | 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

626 | 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

536 | 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

643 | 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]

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]

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]

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

707 | 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

1593 | 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

763 | 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]

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

1193 | 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

1035 | 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

841 | 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]

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

1552 | 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

1275 | 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

780 | 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

877 | 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

1064 | 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]

Cyclin D1 depletion induces DNA damage in mantle cell lymphoma lines

845 | 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

2445 | 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

1475 | 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

2647 | 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]

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

2275 | 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]

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]

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

943 | 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

1354 | 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

855 | 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

1146 | 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]

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

1520 | 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

1585 | 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

1109 | 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]

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

1113 | 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

1068 | 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

1681 | 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

1657 | 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]

Expression and clinical significance of Wee1 in colorectal cancer

1372 | 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]

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

3558 | 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

1827 | 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

1213 | 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]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

8660 | 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]

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

6153 | 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

4172 | 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

4162 | 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

7374 | 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

3778 | 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

6771 | 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

2144 | 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

5032 | 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

2366 | 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

2028 | 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]

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

4830 | 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

2143 | 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]

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

4965 | 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

2300 | 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]

R547 is a potent ATP competitive inhibitor of CDK

2298 | Dec 10 2013

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

Thiazovivin helps in promoting human embryonic stem cell

4730 | 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

2369 | 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

2562 | 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

5007 | 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

2526 | 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

2257 | 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

4781 | 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]

Roscovitine is an experimental drug candidate

2532 | 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

2286 | 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

2886 | 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

5259 | 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

3001 | 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

1504 | 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

5141 | 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

2214 | 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

3011 | 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

2881 | 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

2716 | 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

2267 | 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

1709 | 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

4103 | 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

1867 | 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

2874 | 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

5027 | 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

2694 | 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

4874 | 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

6851 | 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

2419 | 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

4078 | 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.

4929 | 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.

3294 | 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

3086 | 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.

4271 | 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]