化学性质：                                                                                                             

产品描述：                                                                                                            

Fluzoparib (SHR3162) is a potent and orally active PARP1 inhibitor (IC50=1.46±0.72 nM, a cell‐free enzymatic assay) with superior antitumor activity. Fluzoparib selectively inhibits the proliferation of homologous recombination repair (HR)‐deficient cells, and sensitizes both HR‐deficient and HR‐proficient cells to cytotoxic agents. Fluzoparib exhibits good pharmacokinetic properties in vivo and can be used for BRCA1/2-mutant relapsed ovarian cancer research[1].

Fluzoparib (30 μM; 24 hour) increases the levels of γH2AX in a concentration‐dependent manner in both BRCA2‐deficient V‐C8 cells and BRCA1‐deficient MDA‐MB‐436 cells, but not in BRCA‐proficient V‐C8#13‐5 cells[1].Fluzoparib (10 μM; 24 hour) increases levels of both pCDK1 and cyclin B, indicating activation of the G2/M checkpoint in MDA‐MB‐436 cells[1].Fluzoparib (10 μM; 72 hour) increases the processing of caspase‐3, ‐8, and ‐9 concentration‐dependently, it induces G2/M arrest and apoptosis in HR‐deficient MDA‐MB‐436 cells cells[1].Fluzoparib is preferentially efficacious against HR‐deficient cells, such as BRCA1‐deficient (UWB1.289), MDA‐MB‐436, BRCA2‐deficient (V‐C8), BRCA1‐deficientBRCA2‐mutated (MX‐1) and BRCA1 hypermethylated (OVCAR‐8) cells with IC50 values of 0.51 μM, 1.57 μM, 0.053 μM, 1.57 μM, and 1.43 μM, respectively. The IC50 values for HR‐proficient cells (V‐C8#13‐5 and UWB1.289 BRCA1) are both >10 μM[1].

特别提醒：