3L8V

Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor C-MET in complex with a biarylamine based inhibitor

Summary for 3L8V

• Entry DOI: 10.2210/pdb3l8v/pdb
• Descriptor: Hepatocyte growth factor receptor, 2-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}amino)-N-(2,4-difluorophenyl)pyridine-3-carboxamide (3 entities in total)
• Functional Keywords: receptor tyrosine kinase, signal transduction, grb2, shc, atp-binding, glycoprotein, membrane, nucleotide-binding, phosphoprotein, proto-oncogene, transferase, transmembrane, tyrosine-protein kinase, alternative splicing, chromosomal rearrangement, disease mutation, kinase, polymorphism, receptor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein. Isoform 3: Secreted: P08581
• Total number of polymer chains: 1
• Total formula weight: 35886.43

Authors

Sack, J. (deposition date: 2010-01-04, release date: 2010-05-05, Last modification date: 2023-09-06)

Primary citation

Williams, D.K.,Chen, X.T.,Tarby, C.,Kaltenbach, R.,Cai, Z.W.,Tokarski, J.S.,An, Y.,Sack, J.S.,Wautlet, B.,Gullo-Brown, J.,Henley, B.J.,Jeyaseelan, R.,Kellar, K.,Manne, V.,Trainor, G.L.,Lombardo, L.J.,Fargnoli, J.,Borzilleri, R.M.
Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors.
Bioorg.Med.Chem.Lett., 20:2998-3002, 2010

PubMed Abstract: Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model.

PubMed: 20382527
DOI: 10.1016/j.bmcl.2010.01.042

Experimental method

X-RAY DIFFRACTION (2.4 Å)