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Capmatinib dihydrochloride
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Capmatinib dihydrochloride图片
CAS NO:1197376-85-4
包装与价格:
包装价格(元)
100mg电议
250mg电议
500mg电议

产品名称
INC280 dihydrochloride
INCB28060 dihydrochloride
产品介绍
Capmatinib (INC280; INCB28060) dihydrochloride 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 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 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 主要由 CYP3A4 和醛氧化酶代谢。
生物活性

Capmatinib (INC280; INCB28060) dihydrochloride is a potent, orally active, selective, and ATP competitivec-Metkinase inhibitor (IC50=0.13 nM). Capmatinib dihydrochloride 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 potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively inducesapoptosis. Antitumor activity. Capmatinib dihydrochloride is largely metabolized by CYP3A4 and aldehyde oxidase[1][2][3].

IC50& Target

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

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.
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.
Clinical Trial
分子量

485.34

Formula

C23H19Cl2FN6O

CAS 号

1197376-85-4

中文名称

卡马替尼二盐酸盐

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.