Pamiparib (BGB-290)

Pamiparib is an inhibitor of poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 (IC₅₀s = 1.3 and 0.92 nM, respectively).¹ It is selective for PARP1 and PARP2 over PARP3 (IC₅₀ = 0.068 ?M) and other PARP isoforms (IC₅₀s = 2.4->100 ?M), as well as over tankyrase 1 (TNKS1) and TNKS2 (IC₅₀s = 0.23 and 0.14 ?M, respectively). Pamiparib inhibits PARP activity induced by hydrogen peroxide in HeLa cells with an IC₅₀ value of 0.24 nM. It selectively inhibits proliferation of MDA-MB-436 cells expressing mutant BRCA1 and Capan-1 cells expressing mutant BRCA2 (EC₅₀s = 41 and 960 nM, respectively) over MDA-MB-231 cells expressing wild-type BRCA (EC₅₀ = ~9,000 nM). Pamiparib (1.6-6.3 mg/kg twice per day) induces tumor regression in an MDA-MB-436 mouse xenograft model. It also potentiates increases in survival induced by temozolomide in an H209 mouse xenograft model of small cell lung cancer brain metastasis.

1.Xiong, Y., Guo, Y., Liu, Y., et al.Pamiparib is a potent and selective PARP inhibitor with unique potential for the treatment of brain tumorNeoplasia22(9)431-440(2020)