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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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)^[1].
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^[1].
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^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

472.40

C₂₂H₁₆F₄N₆O₂

1358715-18-0

氟唑帕利

Room temperature in continental US; may vary elsewhere.

DMSO : 20.83 mg/mL (44.09 mM; ultrasonic and warming and heat to 60°C)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (4.40 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.40 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.08 mg/mL (4.40 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.40 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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.