• The Aurora kinase enzymes could be potential targets for novel small-molecule enzyme inhibitors. (wikipedia.org)
  • The small molecule compound, Erlotinib is a receptor tyrosine kinase inhibitor (EGFR antagonist) and belongs to molecular targeted therapy Drugs. (lookchem.com)
  • We found that alisertib and danusertib, two small-molecule inhibitors of AURK, are inefficient inducers of apoptosis in HCT116 and DLD-1 colon cancer cells, the survival of which requires at least one of the two antiapoptotic Bcl-2 family proteins, Bcl-xL and Mcl-1. (bvsalud.org)
  • citation needed] Kinome Cyclin-dependent kinase Signal transduction Andrews, Paul D. (wikipedia.org)
  • Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity. (cdc.gov)
  • Kinomic profiling of principal mesangial cells treated with PDGF uncovered activation of many protein-tyrosine kinases, including AXL. (nipponkaigi-tokyo.com)
  • It can inhibit the phosphorylation reaction through competing with adenosine triphosphate to bind to the catalytic region of the receptor tyrosine kinase, thereby blocking the down-proliferation signaling and inhibiting the activity of the tumor cell ligand-dependent HER-1/EGFR, thus achieving the inhibition of the proliferation of tumor cells. (lookchem.com)
  • Alert FDA Approves Bosutinib for Children With CML The agency approved the tyrosine kinase inhibitor for pediatric patients with chronic phase Ph+ chronic myelogenous leukemia that is newly diagnosed or resistant or intolerant to prior therapy. (medscape.com)
  • The mammalian Aurora kinase family contains three serine/threonine kinase members that participate in cell division. (rndsystems.com)
  • The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. (cancerindex.org)
  • A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
  • Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
  • A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)
  • So far three Aurora-kinase inhibitors have been described: ZM447439, hesperadin and VX-680. (wikipedia.org)
  • ZM447439 Hesperadin VX-680 The structure and active site of Aurora-2-adenosine complex has been determined. (wikipedia.org)
  • The inhibition of Aurora kinases in order to arrest mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells has generated significant discussion within the literature. (rcsb.org)
  • The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells. (stembook.org)
  • The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells. (stembook.org)
  • That SP600125 induces endoreduplication signals, promotes tubulin polymerization, a critical process in cell division, and induces delayed apoptosis in leukemia Aurora kinases cells. (hsp90-inhibitors.com)
  • We demonstrate that combination of a Bcl-2 homology (BH)3-mimetic inhibitor (ABT-737), a selective inhibitor of Bcl-xL, Bcl-2, and Bcl-w, with alisertib or danusertib potently induces apoptosis through the Bcl-2 family effector protein Bax. (bvsalud.org)
  • Together, these results define the Bcl-2 protein network critically involved in AURK inhibitor-induced apoptosis and suggest that BH3-mimetics targeting Bcl-xL may help overcome resistance to AURK inhibitors in cancer cells. (bvsalud.org)
  • Alisertib inhibits the interaction between N-myc and its stabilizing factor Aurora-A, inhibiting N-myc signaling, and suppressing tumor growth. (unitn.it)
  • Farnesyltransferase inhibitor tipifarnib is well leurocristine tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic tumor survival pathways in patients with advanced multiple myeloma. (hsp90-inhibitors.com)
  • Aurora kinases, so named because the scattered mitotic spindles generated by mutant forms resemble the Aurora Borealis, have gained a great deal of attention as possible anticancer drug targets. (wikipedia.org)
  • An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
  • Aurora kinases (AURKs) are mitotic kinases important for regulating cell cycle progression. (bvsalud.org)
  • Furthermore, Aurora kinases are known to be oncogenic and overexpressed in various forms of cancerous growth, including leukemia, colon cancer, prostate cancer and breast cancer tumors. (wikipedia.org)
  • Exceptional responders were identified, including complete resolution of liver metastases and prolonged stable disease, with tumors suggestive of N-myc and Aurora-A overactivity. (unitn.it)
  • A genomic network model is used to identify aurora kinase inhibitor-sensitive lung tumors, new Illumina Accelerator start-ups are announced, AI algorithms are being used to improve prostate cancer identification and treatment, and a blood-based DNA methylation test can detect liver cancer. (bio-itworld.com)
  • Mount Sinai researchers have developed a novel method to identify aggressive early-stage lung cancers and target drugs known as aurora kinase inhibitors to tumors that are especially likely to respond. (bio-itworld.com)
  • The Mount Sinai team used a genomics network model to measure tumor invasiveness-distinguishing aggressive tumors from so-called "indolent" ones, which often cannot be told apart via chest CT scan-and identify those that will respond to aurora kinase inhibitors, molecules that can inhibit gene signature regulators. (bio-itworld.com)
  • Some studies have reported that the G2 M arrest induced by SP600125 may be due to inhibition of cyclin B Cdk1 kinase activity through an increase in p21 levels. (hsp90-inhibitors.com)
  • Patient organoids exhibited concordant responses to alisertib and allowed for the dynamic testing of Aurora-N-myc complex disruption. (unitn.it)
  • Conclusions: Although the study did not meet its primary endpoint, a subset of patients with advanced prostate cancer and molecular features supporting Aurora-A and N-myc activation achieved significant clinical benefit from single-agent alisertib. (unitn.it)
  • Ann273, thanks for the info on Alisertib and FGFR status/FGFR inhibitors. (breastcancer.org)
  • The development of the phthalazinone template resulted in a potent Aurora-A selective series of compounds (typically >1000-fold selectivity over Aurora-B) that display good pharmacological profiles with significantly improved oral bioavailability compared to the well studied Aurora inhibitor VX-680. (rcsb.org)
  • In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models. (rcsb.org)
  • Anderson, B.D. Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38α MAP kinase inhibitors with excellent in vivo antiinflammatory properties. (eurekaselect.com)
  • Verapamil is a calcium channel blocker and a potent and orally active first-generation P-glycoprotein (P-gp) inhibitor. (adooq.com)
  • There are three mammalian aurora kinase genes, encoding aurora A, B and C. Intense investigation has focused on aurora A and B as they appear to play a role in oncogenesis with aurora A identified as a low penetrance tumor susceptibility gene in mice and humans. (wikipedia.org)
  • SCARA5 expression is significantly downregulated in various tumor tissues including liver cancer (LC), rectal cancer, and glioblastoma [ 15 , 16 ] and might affect cell proliferation and invasion abilities by the focal adhesion kinase (FAK) signaling pathway and epithelial-mesenchymal transition (EMT) [ 5 , 17 - 20 ]. (hindawi.com)
  • Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION. (lookformedical.com)
  • The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.com)
  • Felodipine is a 1,4-dihydropyridine antagonist and calcium channel protein inhibitor. (adooq.com)
  • The Aurora enzymes are particularly significant because they are involved in a direct path to the nucleosome by phosphorylating histone H3. (wikipedia.org)
  • The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. (cancerindex.org)
  • Aurora A influences centrosome maturation and spindle assembly, while Auroras B and C direct chromosome alignment and segregation. (rndsystems.com)
  • Works in various organisms have revealed that the kinase is involved in centrosome separation, duplication and maturation as well as in bipolar spindle assembly and stability. (lookformedical.com)
  • Aurora kinase inhibitors are a putative drug class for treating cancer. (wikipedia.org)
  • However, their potential is presently compromised by the threat of side effects and by a lack of pharmacological inhibitors of Myc. (nih.gov)
  • Pharmacological response data for targeted inhibitors of SRC, WNT, GSK3b, aurora kinase, PI3 kinase, and mTOR, showed significant differences in sensitivity across cell lines assigned to different subtypes. (tudelft.nl)
  • An AXL-specific inhibitor (bemcentinib) partly blocked PDGF-induced mobile proliferation and decreased phosphorylation of AXL and PDGF receptor as well as the downstream indicators (AKT1 and ERK1/2). (nipponkaigi-tokyo.com)
  • We herein demonstrated that CADM1 interacts with Hippo pathway core kinases and enhances the phosphorylation of YAP1, and also that the membranous co-expression of CADM1 and LATS2 predicts a favorable prognosis in lung adenocarcinoma. (cancerindex.org)
  • These kinases lead to β-catenin stabilization through phosphorylation-dependent inactivation of GSK-3β either directly or indirectly. (lu.se)
  • The research team used a genetically engineered mouse model to define the role of aurora kinases in early progression of the disease. (bio-itworld.com)
  • They identified and tested aurora kinase inhibitors, including AMG900, as an effective treatment to intercept lung cancer progression in the models. (bio-itworld.com)
  • Plant-derived antigen was evaluated to induce FadD32 Inhibitor-1 the mucosal and systemic immune system responses in mice. (mslideas.com)
  • However, overexpression of aurora-A in particular cell lines such as NIH3T3 is sufficient to induce growth on soft agar. (lookformedical.com)
  • We recently showed that NANOG-mediated induction of Aurora A kinase (AURKA), an upstream kinase for aPKCζ, and repression of Lethal Giant Larva 2 (LGL2 or LLGL2), an aPKCζ inhibitor, leads to aPKCζ upregulation and activation. (nature.com)
  • We observed that dexamethasone exposure caused upregulation of Aurora kinase and its various downstream effector kinases such as JAK, p38, mTOR, and S6K. (lu.se)
  • The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)
  • The expression of BCL2 varies in T-ALL depending on its stage of maturation, thereby T-ALL displays a heterogenous response to the BCL2-specific inhibitor venetoclax. (lu.se)
  • Further, second-generation FLT3 inhibitors, such as AC220 and crenolanib, suppressed this signaling both in vitro and in vivo. (lu.se)
  • Cells were cleaned with ice-cold PBS and lysed on glaciers DRAK2-IN-1 with M-PER lysis buffer (Pierce Biotechnology, Inc) supplemented with protease and phosphatase inhibitors (Thermo Fisher Scientific). (nipponkaigi-tokyo.com)
  • PF-07321332 is an orally bioavailable 3C-like protease (3CLPRO) inhibitor. (adooq.com)
  • The hinge (yellow), glycine-rich loop (blue), and activation loop (red) are key features of the protein kinase fold involved in binding adenosine. (wikipedia.org)
  • The protein backbone atoms of residues Glu-211, Ala-213 in the hinge region of Aurora-2, and the sidechain of residue Trp-277, located in the activation loop, bind adenosine through specific hydrogen bonds. (wikipedia.org)
  • abstract = "MK-0457, an Aurora kinase and BCR-ABL inhibitor, was studied on a Phase I/II study in 77 patients with refractory hematologic malignancies. (northwestern.edu)
  • The Aurora kinase family facilitates cell division through various processes and is overexpressed in a wide variety of human cancers, leading to aneuploidy. (usuhs.edu)
  • BrdU cell proliferation assay was performed after incubation with PDGF-AB with or without inhibitors for 22 hours regarding to manufacturers guidelines (Roche Diagnostics). (nipponkaigi-tokyo.com)
  • Fortunately, further studies are underway investigating everything from PARP inhibitors to bispecific T-cell engagers in this challenging setting. (medpagetoday.com)
  • These data suggest KYC is certainly a book and particular inhibitor of MPO activity that's non-toxic to 1353859-00-3 supplier endothelial cell civilizations. (technumber.com)
  • Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)
  • however, the utility of these inhibitors as inducers of cancer cell death has thus far been limited. (bvsalud.org)
  • To build up a new course of MPO inhibitors with reduced toxicity, we synthesized some tripeptides that included both Tyr and Cys. (technumber.com)
  • Etanercept, a dimeric fusion protein that binds TNF, acts as a TNF inhibitor. (adooq.com)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • Jones D, Noble M, Wedge SR, Robson CN, Gaughan L. Aurora A regulates expression of AR-V7 in models of castrate resistant prostate cancer . (ncl.ac.uk)
  • Indeed, we observed partial restoration of dexamethasone sensitivity with a combination of dexamethasone and inhibitors targeting either these kinases or β-catenin. (lu.se)
  • Residues Lys-162 and Asp-274 are essential for Aurora-2 kinase activity but do not hydrogen bond to each other as seen in crystal structures of several other protein kinases. (wikipedia.org)