Capmatinib hydrochloride(free base)

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

卡马替尼盐酸盐是一种有效的、口服活性的、选择性的、ATP 竞争性 c-Met 激酶抑制剂，可有效阻断体外激酶活性 (IC50 = 0.13 nM) 以及细胞内的组成型或 HGF 刺激活性（IC50 值范围为 0.3 至1.1 纳米）。

Capmatinib hydrochloride is a potent orally active selective and ATP competitive c-Met kinase inhibitor?potently blocking in vitro kinase activity (IC50 = 0.13 nM) as well as constitutive or HGF-stimulated activity in cells (IC50 values range from 0.3 to 1.1 nM).

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%, which isreversible and the effect is significantly reduced in several hours after the compound is removed and completely disappeared by 48 hours.Capmatinib (INCB28060) (0-10000 nM; 72 h) inhibits the proliferation of SNU-5, S114, H441 and U-87MG.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.Capmatinib (INCB28060) (0.24-63 nM; over night) prevents HGF-stimulated H441 cell migration.Capmatinib (INCB28060) (0.5-50 nM; 20 min) suppresses phosphorylation of both EGFR and HER-3 rapidly.Capmatinib (INCB28060) (0-333 nM; 24 h) induces apoptosis in SNU-5 cells. Cell Viability Assay 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 IC50 values of 1.2 nM, 12.4 nM, ~0.5 nM and 2 nM, respectively.Cell Migration Assay Cell Line:H441 (stimulated with 50 ng/mL recombinant human HGF for 24h)Concentration:0.24, 1, 4, 16 and 63 nMIncubation Time:Over nightResult:Prevented HGF-stimulated H441 cell migration, with IC50 of approximately 2 nM, and less cell migration at 16 nM.Western Blot Analysis 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 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 Cell Line:SNU-5 cellsConcentration:0.017, 0.15, 1.37, 12.33, 111 and 333 nM Incubation Time:24 h Result:Effectively induced DNA fragmentation.

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.Capmatinib (INCB28060) (0.03-10 mg/kg; PO, single dosage) causes inhibition of c-MET phosphorylation in S114 tumor mice model. Animal Model:Female Balb/c nu/nu mice (inoculated subcutaneously with 5×106 U-87MG glioblastoma cells)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 4×106 S114 tumor cells) 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.

INC280 | INCB28060

Angiogenesis

c-Met/HGFR

c-Met

cancer

cMET Dysegulation Advanced Solid Tumors

1029714-89-3

412.42

C23H17FN6O

>98% (HPLC)

——

Cl.CNC(=O)c1ccc(cc1F)-c1cnc2ncc(Cc3ccc4ncccc4c3)n2n1

——

(-20℃)

With Ice Pack

≥ 2 years