Talazoparib tosylate (C09-1182-763)

Talazoparib tosylate (BMN 673ts) is a novel, potent and orally available PARP1/2 inhibitor with an IC 50 of 0.57 nM for PARP1 .In VitroTalazoparib is a potent PARP1/2 inhibitor (PARP1 IC 50 =0.57 nM), it has no effect on PARG activity at concentrations up to 1 μM. Talazoparib binds to PARP1 with a dissociation constant (K D ) of 0.29 nM. Talazoparib inhibits PARP1 and -2 to a similar extent, with K i s of 1.20 and 0.85 nM, respectively. 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 (MX-1 and SUM149) or BRCA2-deficient (Capan-1) are profoundly sensitive to Talazoparib. Talazoparib induces nuclear γ-H2AX foci at concentrations as low as 100 pM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoTalazoparib is readily orally bioavailable, with more than 40% absolute oral bioavailability in rats when dosed in carboxylmethyl cellulose. Oral administration of Talazoparib 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. Synergistic or additive antitumor effects are also found when Talazoparib is combined with temozolomide, SN38, or platinum drugs . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:IC50: 0.57 nM (PARP1). Specification: ≥99% Molecular Formula: C26H22F2N6O4S Molecular Weight: 552.55 EC Number: 806-564-1 PubChem CID: 135565654 Isomeric SMILES: CC1=CC=C(C=C1)S(=O)(=O)O.CN1C(=NC=N1)[C@@H]2[C@H](NC3=CC(=CC4=C3C2=NNC4=O)F)C5=CC=C(C=C5)F