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Capmatinib

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Chemical Structure| 1029712-80-8 同义名 : INCB28060;INC280;NVP-INC280
CAS号 : 1029712-80-8
货号 : A193720
分子式 : C23H17FN6O
纯度 : 99%+
分子量 : 412.419
MDL号 : MFCD18633285
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(60.62 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 4 mg/mL(9.7 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 The overexpression and activation of the Met receptor and its ligand HGF (hepatocyte growth factor) are associated with a wide variety of human malignancies, as well as the tumor invasion. Capmatinib is a highly selective and potent c-Met inhibitor with IC50 values of 0.13nM (measured by recombinant kinase assays), without direct inhibitory effect on the RONβ, EGFR and HER-3. Cellular study showed a dose-dependent inhibition by Capmatinib against c-MET activation in both cells with constitutively active c-MET, such as SNU-5 (IC50=1.1nM) and S114 (IC50=0.9nM), and cells with HGF-stimulated c-MET, like A549 (IC50=0.7nM), U-87MG (IC50=1nM), 786-0 (IC50=0.6nM), H441 (IC50=0.7nM), H596 (IC50=0.4nM) and H1437 (IC50=0.3nM). Treatment with Capmatinib for 2h at concentration>0.98nM caused significant decreased p-c-MET, and its major downstream effectors, including phosphorylation of ERK1/2 (≥3.91nM), AKT (>0.98nM), FAK (≥3.91nM), GAB1(≥3.91nM), STAT3 (≥0.24nM)/5 (≥0.98nM), in SNU-5 with constitutively active c-MET. Consistent with this, Capmatinib suppressed growth of SNU-5 cells, with IC50 value of 1.2nM and a calculated IC90 value of 4.6nM, in c-Met-dependent manner. Significant apoptosis can be observed in SNU-5 cells treated with Capmatinib at concentration>5nM through DNA fragmentation and cleaved PARP. As prediction, Capmatinib dose-dependently prevented anchorage-independent U-87MG cell growth in soft agar and HGF-stimulated H441 cell migration at concentration ranging in 1-63nM. Though Capmatinib did not directly inhibit the other RTKs in kinase assays, the suppression of p-EGFR and p-HER3 by Capmatinib through cross talk in H1993 cells. Oral administration of Capmatinib at dose of 3, 10 and 30mg/kg for 2 weeks caused tumor growth inhibition dose-dependently in both mice xenograft S114 and U-87MG, with significant c-MET-phosphorylation in vivo[1].
作用机制 Capmatinib is an ATP-competitive c-MET inhibitor.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.42mL

0.48mL

0.24mL

12.12mL

2.42mL

1.21mL

24.25mL

4.85mL

2.42mL