Talazoparib tosylate (BMN 673ts) is an orally active and highly potent PARP1/2 inhibitor with antitumor activity for the study of specific breast cancers.

PARP2:0.85 nM (Ki), PARP1:1.20 nM (Ki)

Talazoparib tosylate had similar inhibitory effects on PARP1 and PARP2 (Ki values of 1.20 nM and 0.85 nM, respectively). Talazoparib tosylate induced the formation of an intranuclear γ-H2AX focus at concentrations as low as 100 pM. Talazoparib tosylate had no effect on PARG activity at concentrations up to 1 μM. The dissociation constant for binding of Talazoparib tosylate to PARP1 was 0.29 nM. Talazoparib tosylate selectively targets tumor cells with defects in the BRCA1, BRCA2 or PTEN genes with 20- to 200-fold greater potency than existing PARP1/2 inhibitors. Talazoparib tosylate specifically targets tumor cells with defects in homologous recombination genes, and tumor models with defects in BRCA1 or BRCA2 defective tumor models are extremely sensitive to Talazoparib tosylate. [1]

Talazoparib tosylate has high oral bioavailability, with absolute bioavailability exceeding 40% when administered orally in rats using carboxymethylcellulose as the vehicle. Talazoparib tosylate has significant antitumor effects when administered orally; Talazoparib tosylate exhibits high potency sensitivity in transplanted tumors with impaired DNA repair due to BRCA mutations or PTEN defects when administered at well-tolerated doses in mice. [1]