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  • A small molecule inhibitor of cell cycle checkpoint kinase 1 (Chk1), with potential chemosensitization activity. Chk1 inhibitor GDC-0575 specifically binds to and inhibits Chk1; this may result in tumor cells bypassing Chk1-dependent cell cycle arrest in the S and G2/M phases, which permits the cells to undergo DNA repair prior to entry into mitosis. Therefore, Chk1 inhibition may sensitize tumor cells to the DNA damaging effects of certain chemotherapeutic agents. Chk1 is an ATP-dependent serine-threonine kinase that phosphorylates cdc25 phosphatases in response to DNA damage. This results in both inhibitory tyrosine phosphorylation of cyclin-dependent kinase (CDK)-cyclin complexes and cell cycle arrest, which facilitates DNA damage repair. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C116845\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C116845\' NCI Thesaurus)
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