For research use only. Not for therapeutic Use.
INCB28060 (Cat No.:I000180) is a selective MET inhibitor used for the treatment of non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations. By inhibiting MET, a receptor tyrosine kinase involved in cellular growth, survival, and migration, INCB28060 disrupts the signaling pathways that drive tumor growth and metastasis. It specifically targets cancers with MET alterations, making it an effective precision therapy for patients with MET-driven cancers. Capmatinib has shown promising clinical efficacy in shrinking tumors and improving progression-free survival in NSCLC patients with these genetic mutations.
| Catalog Number | I000180 |
| CAS Number | 1029712-80-8 |
| Synonyms | 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide |
| Molecular Formula | C23H17FN6O |
| Purity | 98% |
| Target | MET |
| Target Protein | |
| Solubility | DMSO: ≤ 12.66 mg/mL |
| Appearance | Solid |
| Storage | Dry, dark and at 2 - 8 °C for six months or -20°C for two years. |
| IC50 | IC50: 0.13 nM (c-MET) |
| IUPAC Name | 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide |
| InChI | 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) |
| InChIKey | LIOLIMKSCNQPLV-UHFFFAOYSA-N |
| SMILES | CNC(=O)C1=C(C=C(C=C1)C2=NN3C(=CN=C3N=C2)CC4=CC5=C(C=C4)N=CC=C5)F |
| Reference | 1:Clin Cancer Res. 2011 Nov 15;17(22):7127-38. doi: 10.1158/1078-0432.CCR-11-1157. Epub 2011 Sep 14. A novel kinase inhibitor, INCB28060, blocks c-MET-dependent signaling, neoplastic activities, and cross-talk with EGFR and HER-3.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, PMID: 21918175 DOI: 10.1158/1078-0432.CCR-11-1157 </br><span>Abstract:</span> PURPOSE: The c-MET receptor tyrosine kinase plays important roles in the formation, progression, and dissemination of human cancer and presents an attractive therapeutic target. This study describes the preclinical characterization of INCB28060, a novel inhibitor of c-MET kinase.EXPERIMENTAL DESIGN: Studies were conducted using a series of in vitro and in vivo biochemical and biological experiments.RESULTS: 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.CONCLUSIONS: 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. |
