{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Walton MI"],"funding":["Cancer Research UK","Medical Research Council","National Institute for Health Research (NIHR)","Wellcome Trust"],"pagination":["5650-61"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3474704"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(20)"],"pubmed_abstract":["Purpose
Many tumors exhibit defective cell-cycle checkpoint control and increased replicative stress. CHK1 is critically involved in the DNA damage response and maintenance of replication fork stability. We have therefore discovered a novel potent, highly selective, orally active ATP-competitive CHK1 inhibitor, CCT244747, and present its preclinical pharmacology and therapeutic activity.Experimental design
Cellular CHK1 activity was assessed using an ELISA assay, and cytotoxicity a SRB assay. Biomarker modulation was measured using immunoblotting, and cell-cycle effects by flow cytometry analysis. Single-agent oral CCT244747 antitumor activity was evaluated in a MYCN-driven transgenic mouse model of neuroblastoma by MRI and in genotoxic combinations in human tumor xenograft"],"journal":["Clinical cancer research : an official journal of the American Association for Cancer Research"],"pubmed_title":["CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs."],"pmcid":["PMC3474704"],"funding_grant_id":["A10334","A11566","A8274","091763Z/10/Z","C309/A11566","C309/A8274","11566","C1060/A10334"],"pubmed_authors":["Raynaud FI","Box G","Matthews TP","Chesler L","Garrett MD","Eccles SA","Eve PD","Smith EL","Lainchbury M","Hayes A","Valenti MR","Jamin Y","Reader JC","Aherne GW","De Haven Brandon AK","Boxall KJ","Robinson SP","Collins I","Hallsworth A","Walton MI"],"additional_accession":[]},"is_claimable":false,"name":"CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs.","description":"Purpose
Many tumors exhibit defective cell-cycle checkpoint control and increased replicative stress. CHK1 is critically involved in the DNA damage response and maintenance of replication fork stability. We have therefore discovered a novel potent, highly selective, orally active ATP-competitive CHK1 inhibitor, CCT244747, and present its preclinical pharmacology and therapeutic activity.Experimental design
Cellular CHK1 activity was assessed using an ELISA assay, and cytotoxicity a SRB assay. Biomarker modulation was measured using immunoblotting, and cell-cycle effects by flow cytometry analysis. Single-agent oral CCT244747 antitumor activity was evaluated in a MYCN-driven transgenic mouse model of neuroblastoma by MRI and in genotoxic combinations in human tumor xenograft","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Oct","modification":"2026-05-01T23:16:20.782Z","creation":"2019-03-27T00:59:11Z"},"accession":"S-EPMC3474704","cross_references":{"pubmed":["22929806"],"doi":["10.1158/1078-0432.CCR-12-1322","10.1158/1078-0432.ccr-12-1322"]}}