Description: Talazoparib, also known as BMN-673 and MDV-3800, is an orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential antineoplastic activity (PARP1 IC50 = 0.57 nmol/L). BMN-673 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks. BMN-673 has been proven to be highly active in mouse models of human cancer and also appears to be more selectively cytotoxic with a longer half-life and better bioavailability as compared to other compounds in development.
Synonym: BMN673; BMN673; BMN-673; LT673; LT 673; LT-673; MDV-3800; MDV 3800; MDV3800; Talazoparib
IUPAC/Chemical Name: (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one
Name: Talazoparib (BMN-673)
Chemical Formula: C19H14F2N6O
Exact Mass: 380.11972
Molecular Weight: 380.35
Elemental Analysis: C, 60.00; H, 3.71; F, 9.99; N, 22.10; O, 4.21
1: Cardnell RJ, Feng Y, Diao L, Fan YH, Masrorpour F, Wang J, Shen Y, Mills GB, Minna JD, Heymach JV, Byers LA. Proteomic Markers of DNA Repair and PI3K Pathway Activation Predict Response to the PARP Inhibitor BMN 673 in Small Cell Lung Cancer. Clin Cancer Res. 2013 Nov 15;19(22):6322-8. doi: 10.1158/1078-0432.CCR-13-1975. Epub 2013 Sep 27. PubMed PMID: 24077350.
2: Postel-Vinay S, Bajrami I, Friboulet L, Elliott R, Fontebasso Y, Dorvault N, Olaussen KA, AndrÃ© F, Soria JC, Lord CJ, Ashworth A. A high-throughput screen identifies PARP1/2 inhibitors as a potential therapy for ERCC1-deficient non-small cell lung cancer. Oncogene. 2013 Nov 21;32(47):5377-87. doi: 10.1038/onc.2013.311. Epub 2013 Aug 12. PubMed PMID: 23934192.
3: Shen Y, Rehman FL, Feng Y, Boshuizen J, Bajrami I, Elliott R, Wang B, Lord CJ, Post LE, Ashworth A. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin Cancer Res. 2013 Sep 15;19(18):5003-15. doi: 10.1158/1078-0432.CCR-13-1391. Epub 2013 Jul 23. PubMed PMID: 23881923.