INCB28060

• CAT Number: I000180
• CAS Number: 1029712-80-8
• Molecular Formula: C23H17FN6O
• Molecular Weight: 412.4
• Purity: ≥95%
• Target: c-MET
• Solubility: DMSO: ≤ 12.66 mg/mL
• Storage: 3 years -20℃ powder
• IC50: 0.13±0.05 nM( for recombinant human wild-type c-MET) [1]
• 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

INCB28060 (Cat.No:I000180) is a potent and selective inhibitor of the bromodomain and extra-terminal (BET) proteins BRD2, BRD3, and BRD4. It exerts its anti-cancer effects by disrupting the binding of BET proteins to chromatin, thereby inhibiting gene transcription. INCB28060 has shown promise in preclinical studies and is being investigated for its therapeutic potential in various cancers.

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 Abstract: 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.