2014
DOI: 10.1158/1535-7163.mct-13-0803
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Stereospecific PARP Trapping by BMN 673 and Comparison with Olaparib and Rucaparib

Abstract: Anti-poly(ADP-ribose)polymerase (PARP) drugs were initially developed as catalytic inhibitors to block the repair of DNA single-strand breaks. We recently reported that several PARP inhibitors have an additional cytotoxic mechanism by trapping PARP-DNA complexes, and that both olaparib and niraparib act as PARP poisons at pharmacological concentrations. Therefore, we have proposed that PARP inhibitors should be evaluated based both on catalytic PARP inhibition and PARP-DNA trapping. Here, we evaluated the nove… Show more

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Cited by 667 publications
(728 citation statements)
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“…The antitumor activity of PARP inhibitors has been shown to depend on both catalytic PARP inhibition and PARP-DNA trapping (18). Consistent with our findings showing that talazoparib exerts the highest single-agent cytotoxicity of the tested PARP inhibitors, the potency of talazoparib has been attributed to its high efficiency at trapping PARP-DNA complexes (19).…”
Section: Discussionsupporting
confidence: 89%
See 1 more Smart Citation
“…The antitumor activity of PARP inhibitors has been shown to depend on both catalytic PARP inhibition and PARP-DNA trapping (18). Consistent with our findings showing that talazoparib exerts the highest single-agent cytotoxicity of the tested PARP inhibitors, the potency of talazoparib has been attributed to its high efficiency at trapping PARP-DNA complexes (19).…”
Section: Discussionsupporting
confidence: 89%
“…Although different PARP inhibitors were reported to vary in their potency of PARP-DNA trapping (18,19), they have not yet been systematically tested in combination with a range of anticancer drugs in Ewing sarcoma. In addition, little is yet known on cell death signaling pathways that mediate the synergistic interaction of PARP inhibitors and anticancer drugs.…”
Section: Sk-es-mentioning
confidence: 99%
“…Talazoparib BMN 673 is a potent oral PARP 1 and PARP 2 inhibitor [Shen et al 2013;Murai et al 2014]. Toxicities of this agent are similar to other PARP inhibitors but BMN 673 has the added side effect of alopecia, which was observed in the phase I study [Shen et al 2013].…”
Section: Veliparibmentioning
confidence: 99%
“…Talazoparib is a novel and potent PARP inhibitor with a dual effect on PARP catalytic activity and PARP trapping [58]. In a phase 1 study of 100 patients with advanced solid tumours with DNA repair pathway defects, responses were observed in patients with BRCA mutated breast cancer, ovarian cancer and patients with SCLC.…”
Section: Talazoparibmentioning
confidence: 99%