| Identification | Back Directory | [Name]
INCB28060 | [CAS]
1029714-89-3 | [Synonyms]
Capmatinib xHCl
Capmatinib hydrochloride(free base)
Apoptosis,c-Met/HGFR,ATP competitive,inhibit,INC-280,Inhibitor,Capmatinib,SNU-5,INCB-28060,INC 280,Capmatinib xHCl,INCB 28060,H441,Balb/c nu/nu mice,U-87MG,S114,orally active | [Molecular Formula]
C23H18ClFN6O | [MOL File]
1029714-89-3.mol | [Molecular Weight]
448.89 |
| Hazard Information | Back Directory | [Uses]
Capmatinib (INC280; INCB28060) hydrochloride is a potent, orally active, selective, and ATP competitive c-Met kinase inhibitor (IC50=0.13 nM). Capmatinib hydrochloride 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 hydrochloride potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis. Antitumor activity. Capmatinib hydrochloride is largely metabolized by CYP3A4 and aldehyde oxidase[1][2][3]. | [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 5×106 U-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 4×106 S114 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. |
| [References]
[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. DOI:10.1158/1078-0432.CCR-11-1157
[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. DOI:10.1158/1078-0432.CCR-18-2814
[3] Dhillon S. Capmatinib: First Approval. Drugs. 2020 Jul;80(11):1125-1131. DOI:10.1007/s40265-020-01347-3 |
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| Company Name: |
InvivoChem
|
| Tel: |
13549236410 |
| Website: |
https://www.invivochem.cn/ |
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