Talazoparib tosylate is a novel and potent PARP1/2 (n IC50: 0.57 nM for PARP1).

Talazoparib inhibits PARP1 and -2 to a similar extent (Kis: 1.20 and 0.85 nM, respectively). Talazoparib induces nuclear γ-H2AX foci at concentrations as low as 100 pM. Talazoparib has no effect on PARG activity at concentrations up to 1 μM. Talazoparib binds to PARP1 with a dissociation constant of 0.29 nM. Talazoparib selectively targets tumor cells with BRCA1, BRCA2, or PTEN gene defects with 20- to more than 200-fold greater potency than existing PARP1/2 inhibitors. Talazoparib targets tumor cells with homologous recombination gene defects. Tumor models that are either BRCA1-deficient or BRCA2-deficient are profoundly sensitive to Talazoparib. [1].

Talazoparib is readily orally bioavailable, with more than 40% absolute oral bioavailability in rats when dosed in carboxymethyl cellulose. Talazoparib (p.o.) elicits remarkable antitumor activity; xenografted tumors that carry defects in DNA repair due to BRCA mutations or PTEN deficiency are profoundly sensitive to oral Talazoparib treatment at well-tolerated doses in mice [1].

1373431-65-2

C26H22F2N6O4S

552.55

BMN 673ts

DMSO:108 mg/mL (195.46 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years