INCB28060 is an orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor INCB28060 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. Capmatinib was approved in 2020.
CAS Number: 1029712-80-8
Molecular Weight: 412.42
Chemical Name: 2-fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide
Appearance: Solid Power
Purity: ≥98% (or refer to the Certificate of Analysis)
Solubility: Soluble in DMSO, not in water
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis
Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.
Shelf Life: ≥12 months if stored properly.
Stock Solution Storage: 0 - 4 oC for 1 month or refer to the Certificate of Analysis.
Drug Formulation: To be determined.
HS Tariff Code: 382200
How to use
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%. INCB28060 inhibits SNU-5 viability or proliferation with an average IC50 value of 1.2 nM and a calculated IC90 value of 4.6 nM INCB28060 prevents HGF-stimulated H441 cell migration, with IC50 of approximately 2 nM. Again, there is little cell migration at a concentration of 16 nM INCB28060. INCB28060 potently and specifically inhibits c-MET enzyme activity, c-MET-mediated signal transduction, and the c-MET-dependent neoplastic phenotype of tumor cells. INCB28060 exhibits strong antitumor activity in c-MET-dependent tumor models at well-tolerated doses. INCB28060 exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10, 000-fold selectivity over a large panel of human kinases. INCB28060 potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis.
Oral dosing of INCB28060 results in time- and dose-dependent inhibition of c-MET phosphorylation and tumor growth in c-MET-driven mouse tumor models, and the inhibitor is well tolerated at doses that achieve complete tumor inhibition. Furthermore, once daily dosing of 10 mg/kg INCB28060 results in partial regressions in 6 of 10 U-87MG tumor-bearing mice. It is noted that in both S114 and U-87MG models, tumor growth inhibition increases with increased exposure of the compound and that tumor regressions could only be achieved when the compound exposure consistently exceeded 90% of c-MET inhibition. In these studies, INCB28060 is well tolerated at all doses during the treatment periods, with no evidence of overt toxicity or weight loss.
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