Pamiparib (BGB-290) is an orally active, potent, highly selective PARP inhibitor with IC50 values of 0.9 nM for PARP1 and 0.5 nM for PARP2. It exhibits strong PARP trapping, has the capability to penetrate the brain, and is used for researching various cancers, including solid tumors.

PARP1:0.9 nM, PARP2:0.5 nM

Pamiparib, an investigational Poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development, demonstrates excellent selectivity for both PARP1 and PARP2, and superb anti-proliferation activities in tumor cell lines with BRCA1/2 mutations or HR pathway deficiency (HRD).?Pamiparib has good bioavailability and is 16-fold more potent than olaparib in an efficacy study using BRCA1 mutated MDA-MB-436 breast cancer xenograft model.?Pamiparib also shows strong anti-tumor synergy with temozolomide (TMZ), a DNA alkylating agent used to treat brain tumors.?Compared to other PARP inhibitors, pamiparib demonstrated improved penetration across the blood brain barrier (BBB) in mice.?Oral administration of pamiparib at a dose as low as 3 mg/kg is sufficient to abrogate PARylation in brain tumor tissues.?In SCLC-derived, TMZ-resistant H209 intracranial xenograft model, combination of pamiparib with TMZ overcomes its resistance and shows significant tumor inhibitory effects and prolonged life span[1].