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). Talazoparib acts as an inhibitor of poly ADP ribose polymerase(PARP) which aids in single strand DNA repair. Cells that have BRCA1/2 mutations are susceptible to the cytotoxic effects of PARP inhibitors because of an accumulation of DNA damage. Talazoparib is theorized to have a higher potency than olaparib due to the additional mechanism of action called PARP trapping. PARP trapping is the mechanism of action where the PARP molecule is trapped on the DNA, which interferes with the cells ability to replicate. Talazoparib is found to be ~100 fold more efficient in PARP trapping than olaparib
Wang, Bing; Chu, Daniel; Feng, Ying; Shen, Yuqiao; Aoyagi-Scharber, Mika; Post, Leonard E. Journal of Medicinal Chemistry. Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1/2 Inhibitor, as an Anticancer Agent. Journal of Medicinal Chemistry. Volume 59. Issue 1. Pages 335-357. Journal; Online Computer File. (2016).
Xu, Yong; Yohi, Peter W.; Xu, Michael; Cruise, Douglas; Huang, Lu. Preparation of PARP inhibitor talazoparib and intermediates thereof. Assignee Guangzhou Wellhealth Bio-Pharmaceutical Co., Ltd., Peop. Rep. China; Guangzhou Bio Blue Technology Co., Ltd. WO 2017215166. (2017).
Henderson, Mark. Process for the preparation of triazole intermediates useful in the synthesis of protected N-alkyltriazolecarbaldehydes. Assignee BioMarin Pharmaceutical Inc., USA. WO 2015069851. (2015).
Wang, Bing; Chu, Daniel. Dihydropyridophthalazinone derivatives as poly(ADP-ribose)polymerase (PARP) inhibitors and their preparation and use for the treatment of cancer. Assignee BioMarin Pharmaceutical Inc., USA. WO 2011130661. (2011).
