{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Murai J"],"funding":["CCR NIH HHS","Intramural NIH HHS","NCI NIH HHS"],"pagination":["408-16"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4019318"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["349(3)"],"pubmed_abstract":["We recently showed that poly(ADP-ribose) polymerase (PARP) inhibitors exert their cytotoxicity primarily by trapping PARP-DNA complexes in addition to their NAD(+)-competitive catalytic inhibitory mechanism. PARP trapping is drug-specific, with olaparib exhibiting a greater ability than veliparib, whereas both compounds are potent catalytic PARP inhibitors. Here, we evaluated the combination of olaparib or veliparib with therapeutically relevant DNA-targeted drugs, including the topoisomerase I inhibitor camptothecin, the alkylating agent temozolomide, the cross-linking agent cisplatin, and the topoisomerase II inhibitor etoposide at the cellular and molecular levels. We determined PARP-DNA trapping and catalytic PARP inhibition in genetically modified chicken lymphoma DT40, human prostate"],"journal":["The Journal of pharmacology and experimental therapeutics"],"pubmed_title":["Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition."],"pmcid":["PMC4019318"],"funding_grant_id":["HHSN261200800001E","HHSN261200800001C","Z01 BC006150"],"pubmed_authors":["Doroshow JH","Pommier Y","Takeda S","Murai J","Zhang Y","Morris J","Ji J"],"additional_accession":[]},"is_claimable":false,"name":"Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition.","description":"We recently showed that poly(ADP-ribose) polymerase (PARP) inhibitors exert their cytotoxicity primarily by trapping PARP-DNA complexes in addition to their NAD(+)-competitive catalytic inhibitory mechanism. PARP trapping is drug-specific, with olaparib exhibiting a greater ability than veliparib, whereas both compounds are potent catalytic PARP inhibitors. Here, we evaluated the combination of olaparib or veliparib with therapeutically relevant DNA-targeted drugs, including the topoisomerase I inhibitor camptothecin, the alkylating agent temozolomide, the cross-linking agent cisplatin, and the topoisomerase II inhibitor etoposide at the cellular and molecular levels. We determined PARP-DNA trapping and catalytic PARP inhibition in genetically modified chicken lymphoma DT40, human prostate","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Jun","modification":"2025-04-21T18:59:21.711Z","creation":"2019-03-27T01:28:06Z"},"accession":"S-EPMC4019318","cross_references":{"pubmed":["24650937"],"doi":["10.1124/jpet.113.210146"]}}