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MedKoo CAT#: 205494
CAS#: 1029712-80-8 (free base)
Description: Capmatinib, also known as INCB28060 and INC280, is an orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor INC280 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.
MedKoo Cat#: 205494
CAS#: 1029712-80-8 (free base)
Chemical Formula: C23H17FN6O
Exact Mass: 412.14479
Molecular Weight: 412.42
Elemental Analysis: C, 66.98; H, 4.15; F, 4.61; N, 20.38; O, 3.88
Related CAS #: 1029712-80-8 (free base) 1029714-89-3 (XHCl) 1197376-85-4 (2HCl)
Synonym: INC280; INC-280; INC 280; INCB028060; INCB-028060; INCB 028060; INCB28060; INCB-28060; INCB 28060; Capmatinib.
IUPAC/Chemical Name: 2-fluoro-N-methyl-4-(7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl)benzamide
InChi Key: LIOLIMKSCNQPLV-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H17FN6O/c1-25-22(31)18-6-5-16(11-19(18)24)21-13-28-23-27-12-17(30(23)29-21)10-14-4-7-20-15(9-14)3-2-8-26-20/h2-9,11-13H,10H2,1H3,(H,25,31)
SMILES Code: O=C(NC)C1=CC=C(C2=NN3C(N=C2)=NC=C3CC4=CC=C5N=CC=CC5=C4)C=C1F
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. This inhibitor potently blocks c-MET phosphorylation and activation of its key downstream effectors in c-MET-dependent tumor cell lines. As a result, INCB28060 potently inhibits c-MET-dependent tumor cell proliferation and migration and effectively induces apoptosis in vitro. 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. In a further exploration of potential interactions between c-MET and other signaling pathways, we found that activated c-MET positively regulates the activity of epidermal growth factor receptors (EGFR) and HER-3, as well as expression of their ligands. These effects are reversed with INCB28060 treatment. Finally, we confirmed that circulating hepatocyte growth factor levels are significantly elevated in patients with various cancers. Activated c-MET has pleiotropic effects on multiple cancer-promoting signaling pathways and may play a critical role in driving tumor cell growth and survival. INCB28060 is a potent and selective c-MET kinase inhibitor that may have therapeutic potential in cancer treatment. (source: Clin Cancer Res; 17(22); 7127-38. Â©2011 AACR.)
1: Liu X, Wang Q, Yang G, Marando C, Koblish HK, Hall LM, Fridman JS, Behshad E, Wynn R, Li Y, Boer J, Diamond S, He C, Xu M, Zhuo J, Yao W, Newton RC, Scherle PA. 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. Epub 2011 Sep 14. PubMed PMID: 21918175.