Capmatinib

SKU: orb1227116

Description

Capmatinib (INCB-28060, INC-280) is a highly potent, selective, ATP competitive inhibitor of c-MET kinase with IC50 of 0.13 nM, displays no activity against RONβ, EGFR and HER-3; inhibits c-MET phosphorylation (IC50=1 nM) in SNU-5 human gastric cancer cell line, is slightly more potent in H596 and H1437 lung cancer cell lines that express mutant c-MET due to an exon 14 deletion and a R988C mutation; inhibits c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models.Lung Cancer Phase 3 Clinical(In Vitro):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 is reversible 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.(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.Capmatinib (INCB28060) (0.03-10 mg/kg; PO, single dosage) causes inhibition of c-MET phosphorylation in S114 tumor mice model.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 1029712-80-8
• MW: 412.42
• Purity: >98% (HPLC)
• Formula: C₂₃H₁₇FN₆O
• SMILES: CNC(=O)C1=C(F)C=C(C=C1)C1=NN2C(CC3=CC4=C(C=C3)N=CC=C4)=CN=C2N=C1
• Target: c-Met/HGFR
• Solubility: DMSO: 12.66 mg/mL

Bioactivity

• In Vivo:
  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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

INCB28060 | INCB-28060 | INC-280 | INC280

Quick Database Links

Gene Symbol

c-Met/HGFR