Capmatinib (INC280; INCB28060) is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC₅₀=0.13 nM). Capmatinib (INC280; INCB28060) potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity^[1][2].

IC50: 0.13 nM (c-MET)^[1]

Capmatinib (INCB28060) inhibits c-MET phosphorylation with an IC₅₀ value of approximately 1 nM and a concentration of approximately 4 nM inhibits c-MET more than 90%. Capmatinib (INCB28060) inhibits SNU-5 viability or proliferation with an average IC₅₀ value of 1.2 nM and a calculated IC₉₀ value of 4.6 nM Capmatinib (INCB28060) prevents HGF-stimulated H441 cell migration, with IC₅₀ of approximately 2 nM. Again, there is little cell migration at a concentration of 16 nM Capmatinib (INCB28060). Capmatinib (INCB28060) potently and specifically inhibits c-MET enzyme activity, c-MET-mediated signal transduction, and the c-MET-dependent neoplastic phenotype of tumor cells. Capmatinib (INCB28060) exhibits strong antitumor activity in c-MET-dependent tumor models at well-tolerated doses. Capmatinib (INCB28060) exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10,000-fold selectivity over a large panel of human kinases. Capmatinib (INCB28060) potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis^[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.

Oral dosing of Capmatinib (INCB28060) results in time- and dose-dependent inhibition of c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models, and the inhibitor is well tolerated at doses that achieve complete tumor inhibition. Furthermore, once daily dosing of 10 mg/kg Capmatinib (INCB28060) results in partial regressions in 6 of 10 U-87MG tumor-bearing mice. It is noted that in both S114 and U-87MG models, tumor growth inhibition increases with increased exposure of the compound and that tumor regressions could only be achieved when the compound exposure consistently exceeded 90% of c-MET inhibition. In these studies, Capmatinib (INCB28060) is well tolerated at all doses during the treatment periods, with no evidence of overt toxicity or weight loss^[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.

412.42

C₂₃H₁₇FN₆O

1029712-80-8

卡马替尼；苯扎米特

Room temperature in continental US; may vary elsewhere.

DMSO : 25 mg/mL (60.62 mM; Need ultrasonic)

H₂O : 10 mg/mL (24.25 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: ≥ 2.08 mg/mL (5.04 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.04 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% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (5.04 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (5.04 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 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Liu X, et al. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clin Cancer Res. 2011 Nov 15;17(22):7127-38.

  [2]. Baltschukat S, et al. Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation. Clin Cancer Res. 2019 May 15;25(10):3164-3175.

Optimal cell density used in the viability assay is predetermined for individual cell lines. To determine compound potency, cells are seeded into 96-well microplates at the appropriate density in media containing 1% to 2% FBS and supplemented with serial dilutions of Capmatinib (INCB28060) in a final volume of 100 μL per well. After 72 hour incubation, 24 μL of CellTiter 96 AQueous One Solution is added to each well, and the plates are incubated for 2 hours in a 37°C incubator. The optical density is measured in the linear range using a microplate reader at 490 nm with wavelength correction at 650 nm. IC₅₀ values are calculated using the GraphPad Prism Software^[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.

Mice^[1]
Tumor-bearing mice are dosed orally, twice each day with 1, 3, 10, or 30 mg/kg of free base Capmatinib (INCB28060) reconstituted in 5% DMAC in 0.5% methylcellulose for up to 2 weeks. Body weights are monitored throughout the study as a gross measure of toxicity/morbidity. Tumor growth inhibition, expressed in percent, is calculated using the formula: (1−[(volume (treated)/volume (vehicle)])×100.

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.

• [1]. Liu X, et al. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3. Clin Cancer Res. 2011 Nov 15;17(22):7127-38.

  [2]. Baltschukat S, et al. Capmatinib (INC280) Is Active Against Models of Non-Small Cell Lung Cancer and Other Cancer Types with Defined Mechanisms of MET Activation. Clin Cancer Res. 2019 May 15;25(10):3164-3175.