PHA-665752 is a selective, ATP-competitive, and active-site inhibitor of the catalytic activity of c-Met kinase (K_i=4 nM; IC₅₀=9 nM). PHA-665752 exhibits >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. PHA-665752 induces apoptosis and cell cycle arrest, and exhibits cytoreductive antitumor activity^[1][2].

Ki: 4 nM^[1]
IC50: 9 nM (c-Met)^[1]

PHA-665752 is a potent and ATP-competitive inhibitor of c-Met kinase activity with a K_i of 4 nM and an IC₅₀ of 9 nM^[1].
PHA-665752 exhibits >50-fold selectivity for c-Met enzyme compared with the majority of kinases evaluated^[1].
PHA-665752 shows potent inhibition of c-Met RTK autophosphorylation in NIH3T3 cells engineered to express high levels of c-Met and hepatocyte growth factor (HGF)^[1].
PHA-665752 inhibits HGF-stimulated or constitutive phosphorylation of mediators of downstream of c-Met such as Gab-1, ERK, Akt, STAT3, PLC-γ, and FAK in multiple tumor cell lines^[1].
PHA-665752 (0-1.25 μM; 18 hours) potently inhibits HGF and c-Met-driven phenotypes such as cell growth (proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells^[1].
PHA-665752 (0-1.25 μM; 72 hours) induces apoptosis in both the presence and absence of HGF at concentrations that inhibited tyrosine phosphorylation of c-Met in GTL-16 cells^[1].
PHA-665752 (0.0125-0.2 μM; 4 hours) potent inhibits HGF-induced c-Met phosphorylation in A549 cells^[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.

PHA-665752 (7.5-30 mg/kg/day; i.v. ; for 9 days) exhibits statistically significant dose-dependent tumor growth inhibition of 68%, 39%, and 20% of vehicle control at the 30 mg/kg/day, 15 mg/kg/day, and 7.5 mg/kg/day doses, respectively^[1].
PHA-665752 shows a potent cytoreductive activity in a gastric carcinoma xenograft model^[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.

641.61

C₃₂H₃₄Cl₂N₄O₄S

477575-56-7

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL (77.93 mM; Need ultrasonic)

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: ≥ 2.5 mg/mL (3.90 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.90 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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: ≥ 2.5 mg/mL (3.90 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (3.90 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Christensen JG, et al. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res. 2003 Nov 1;63(21):7345-55.

  [2]. Ma PC. et al. A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin. Clin Cancer Res. 2005 Mar 15;11(6):2312-9.