4XMO: Crystal structure of c-Met in complex with (R)-5-(8-fluoro-3-(1-fluoro-1-(3-methoxyquinolin-6-yl)ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-methylisoxazole

The overexpression of c-Met and/or hepatocyte growth factor (HGF), the amplification of the MET gene, and mutations in the c-Met kinase domain can activate signaling pathways that contribute to cancer progression by enabling tumor cell proliferation, survival, invasion, and metastasis. Herein, we report the discovery of 8-fluorotriazolopyridines as inhibitors of c-Met activity. Optimization of the 8-fluorotriazolopyridine scaffold through the combination of structure-based drug design, SAR studies, and metabolite identification provided potent (cellular IC50 < 10 nM), selective inhibitors of c-Met with desirable pharmacokinetic properties that demonstrate potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.
PDB ID: 4XMODownload
MMDB ID: 127761
PDB Deposition Date: 2015/1/14
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 1.75  Å
Source Organism:
Similar Structures:
Biological Unit for 4XMO: monomeric; determined by author and by software (PISA)
Molecular Components in 4XMO
Label Count Molecule
Protein (1 molecule)
Hepatocyte Growth Factor Receptor(Gene symbol: MET)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB