Fluzoparib (SHR3162) 是一种有效的口服活性 PARP1 抑制剂(IC₅₀=1.46±0.72  nM)，具有优越的抗肿瘤活性。Fluzoparib 选择性地抑制同源重组修复 (HR) 缺陷细胞的增殖，并使 HR 缺陷细胞对细胞毒性药物敏感。Fluzoparib 在体内具有良好的药代动力学特性，可用于癌症研究。

Fluzoparib (SHR3162) is a potent and orally active PARP1 inhibitor (IC 50 =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.

Solid

PARP-1 1.46±0.72  nM (IC50)

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 ‐deficient BRCA2 ‐mutated (MX‐1) and BRCA1  hypermethylated (OVCAR‐8) cells with IC50 values

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 Cisplati

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[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.

In Vitro: DMSO : 20.83 mg/mL (44.09 mM; ultrasonic and warming and heat to 60°C)配制储备液