Capmatinib (INC280; INCB28060) dihydrochloride hydrate 是一种有效的、口服活性的、选择性的、ATP 竞争性的c-Met激酶抑制剂 (IC50=0.13 nM)。Capmatinib dihydrochloride hydrate 可抑制 c-MET 的磷酸化，以及 c-MET 通路下游效应蛋白如 ERK1/2、AKT、FAK、GAB1 和 STAT3/5。Capmatinib dihydrochloride hydrate 有效抑制 c-Met 依赖性肿瘤细胞的增殖和迁移，并有效诱导细胞凋亡。在肿瘤小鼠模型中表现出抗肿瘤活性。Capmatinib dihydrochloride hydrate 主要由 CYP3A4 和醛氧化酶代谢。
| 生物活性 | Capmatinib (INC280; INCB28060) dihydrochloride hydrate is a potent, orally active, selective, and ATP competitivec-Metkinase inhibitor (IC50=0.13 nM). Capmatinib dihydrochloride hydrate can inhibit phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2,AKT,FAK, GAB1, and STAT3/5. Capmatinib dihydrochloride hydrate potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively inducesapoptosis. Antitumor activity. Capmatinib dihydrochloride hydrate is largely metabolized by CYP3A4 and aldehyde oxidase[1][2][3]. |
体外研究
(In Vitro) | Capmatinib (INCB28060) inhibits c-MET phosphorylation with an IC50value of approximately 1 nM and a concentration of approximately 4 nM inhibits c-MET more than 90%, which is reversible and the effect is significantly reduced in several hours after the compound is removed and completely disappeared by 48 hours[1].
Capmatinib (INCB28060) (0-10000 nM; 72 h) inhibits the proliferation of SNU-5, S114, H441 and U-87MG[1].
Capmatinib (INCB28060) (0.06-62.25 nM; 2h) effectively inhibits phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5[1].
Capmatinib (INCB28060) (0.24-63 nM; over night) prevents HGF-stimulated H441 cell migration[1].
Capmatinib (INCB28060) (0.5-50 nM; 20 min) suppresses phosphorylation of both EGFR and HER-3 rapidly[1].
Capmatinib (INCB28060) (0-333 nM; 24 h) induces apoptosis in SNU-5 cells[1].
Cell Viability Assay[1] | Cell Line: | SNU-5, S114, H441 and U-87MG | | Concentration: | 0-10000 nM | | Incubation Time: | 72 h | | Result: | Inhibited the cell viability of SNU-5 and S114, as well as the colony formation of H441 and U-87MG, with IC50values of 1.2 nM, 12.4 nM, ~0.5 nM and 2 nM, respectively. |
Cell Migration Assay[1] | Cell Line: | H441 (stimulated with 50 ng/mL recombinant human HGF for 24h) | | Concentration: | 0.24, 1, 4, 16 and 63 nM | | Incubation Time: | Over night | | Result: | Prevented HGF-stimulated H441 cell migration, with IC50of approximately 2 nM, and less cell migration at 16 nM. |
Western Blot Analysis[1] | Cell Line: | SNU-5 | | Concentration: | 0.06, 0.24, 0.98, 3.91, 15.63 and 62.25 nM | | Incubation Time: | 2 h | | Result: | Effectively inhibited phosphorylation of c-MET as well as c-MET pathway downstream effectors such as ERK1/2, AKT, FAK, GAB1, and STAT3/5. |
Western Blot Analysis[1] | Cell Line: | H1993 cells | | Concentration: | 0.5, 5 and 50 nM | | Incubation Time: | 20 min | | Result: | Suppressed phosphorylation of both EGFR and HER-3 rapidly and as effectively as the compound inhibited c-MET phosphorylation in H1993 cells. |
Apoptosis Analysis[1] | Cell Line: | SNU-5 cells | | Concentration: | 0.017, 0.15, 1.37, 12.33, 111 and 333 nM | | Incubation Time: | 24 h | | Result: | Effectively induced DNA fragmentation. |
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体内研究
(In Vivo) | Capmatinib (INCB28060) (1-30 mg/kg; PO, twice daily, for 2 weeks) exhibits dose-dependent inhibition of tumor growth, and shows well tolerance at all doses during the treatment periods, with no evidence of overt toxicity or weight loss in U-87MG tumor mice model[1].
Capmatinib (INCB28060) (0.03-10 mg/kg; PO, single dosage) causes inhibition of c-MET phosphorylation in S114 tumor mice model[1].
| Animal Model: | Female Balb/c nu/nu mice (inoculated subcutaneously with 5×106U-87MG glioblastoma cells)[1] | | Dosage: | 1, 3, 10 and 30 mg/kg | | Administration: | PO, twice daily, for 2 weeks | | Result: | Exhibited dose-dependent inhibition of tumor growth with 35% and 76% at 1 and 3 mg/kg once daily; resulted in partial regressions in 6 of 10 U-87MG tumor-bearing mice at 10 mg/kg once daily; and showed well tolerance at all doses during the treatment periods, with no evidence of overt toxicity or weight loss. |
| Animal Model: | Female Balb/c nu/nu mice (inoculated subcutaneously with 4×106S114 tumor cells)[1] | | Dosage: | 0.03, 0.1, 0.3, 1, 3 and 10 mg/kg | | Administration: | PO, single dosage | | Result: | Caused approximately 50% and 90% inhibition of c-MET phosphorylation at 0.03 and 0.3 mg/kg after administration of 30 min, and inhibition of phospho-c-MET exceeded 90% after 7 hours. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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