• 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

• 靶点： PARP-1:1.46±0.72 nM (IC50)

• 体外研究： 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.
  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.
  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.
  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.

• 体内研究： Fluzoparib (oral gavage; 0.3, 1, or 3 mg/kg; single dose) exhibits a good pharmacokinetic profile in Female Balb/cA nude mice (5‐6 weeks old) mice bearing MDA‐MB‐436. After a single oral dose, fluzoparib is rapidly absorbed and rapidly cleared from blood at all dose levels; plasma concentrations of fluzoparib quickly reaches maximum within 2 hours. In contrast, concentrations of fluzoparib in tumor remains at high levels even at 24 hours after dosing (57.9 ng/g , 39.3 ng/g, and 85.6 ng/g for doses of 0.3, 1, and 3 mg/kg, respectively).
  Fluzoparib (oral gavage; 30 mg/kg; 21 days) apparently inhibits the growth of tumor with an inhibition rate of 59% (day 21) at 30 mg/kg, and it does not cause significant loss of body weight in Nude mice bearing MDA‐MB‐436 (BRCA1‐deficient) model.
  Fluzoparib (3mg/kg) combines with Cisplatin, Paclitaxel, or Apatinib (oral gavage; BID; 21 days) causes growth inhibition with rates of 61.4%, 55.3%, and 72.8%, respectively.
  Fluzoparib, Cisplatin, and Apatinib combination or Fluzoparib, Paclitaxel, and Apatinib combination can cause growth inhibition with rates of 84.9% and 75.6% (day 21), respectively in vivo.
  The 2‐drug combination of Fluzoparib with cisplatin and The 3‐drug Fluzoparib, Cisplatin, and Apatinib combination lead to loss of body weight, whereas no apparent toxicity was observed in other combinations.

• 参考文献：
  1. Lei Wang, et al. Pharmacologic characterization of fluzoparib, a novel poly(ADP-ribose) polymerase inhibitor undergoing clinical trials. Cancer Sci. 2019 Mar;110(3):1064-1075. 2. Huiping Li, et al. Phase I dose-escalation and expansion study of PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors. Chin J Cancer Res. 2020 Jun;32(3):370-382.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.117 ml	10.584 ml	21.168 ml
  5 mM	0.423 ml	2.117 ml	4.234 ml
  10 mM	0.212 ml	1.058 ml	2.117 ml
  50 mM	0.042 ml	0.212 ml	0.423 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *