Simmiparib

Simmiparib is a highly potent and orally active PARP1 and PARP2 inhibitor with IC₅₀ values of 1.75 nM and 0.22 nM, respectively. Simmiparib has more potent PARP1/2 inhibition than its parent Olaparib (HY-10162). Simmiparib induces DNA double-strand breaks (DSB) accumulation and G2/M arrest in homologous recombination repair (HR)-deficient cells, thereby inducing apoptosis. Simmiparib exhibits remarkable anticancer activities in cells and nude mice bearing xenografts^[1]. In Vitro:Simmiparib (0-10 μM; 3 days) exhibits anti-proliferative activity against various cancer cells^[1].
Simmiparib (0-10 μM; 48 h) induces typical G2/M arrest in Capan-1 cells^[1].
Simmiparib (0.1-2 μM; 24 h) induces apoptosis in MDA-MB-436 and V-C8 (BRCA2^-/-) cells, and increases dose-dependently the levels of γH2AX^[1].
Simmiparib (1-10 μM; 48 h or 72 h) increases the phosphorylation levels of Chk1 and Chk2 and the protein levels of p-Cyclin B1 (S147), Cyclin B1, p-CDK1 (Y15) and CDK1^[1]. In Vivo:Simmiparib (2, 4 and 8 mg/kg; p.o.; qd, for 14 days) inhibits the growth of tumor in V-C8 (BRCA2^-/-) and MDA-MB-436 (BRCA2^-/-) xenograft mice models^[1].
Simmiparib (10 and 50 mg/kg; p.o.; qd, for 42 days) inhibits the growth of BRCA1-mutated breast cancer in xenograft mice model^[1].