3CTH

Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-met in complex with a aminopyridine based inhibitor

Summary for 3CTH

• Entry DOI: 10.2210/pdb3cth/pdb
• Related: 3C1X 3CTJ 3CTK
• Descriptor: Hepatocyte growth factor receptor, N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamide (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
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P08581
• Total number of polymer chains: 1
• Total formula weight: 35833.39

Authors

Sack, J. (deposition date: 2008-04-14, release date: 2008-06-10, Last modification date: 2024-02-21)

Primary citation

Cai, Z.-W.,Wei, D.,Schroeder, G.M.,Cornelius, L.A.,Kim, K.,Chen, X.-T.,Schmidt, R.J.,Williams, D.K.,Tokarski, J.S.,An, Y.,Sack, J.S.,Manne, V.,Kamath, A.,Zhang, Y.,Marathe, P.,Hunt, J.T.,Lombardo, L.J.,Fargnoli, J.,Borzilleri, R.M.
Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors
Bioorg.Med.Chem.Lett., 18:3224-3229, 2008

PubMed Abstract: A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.

PubMed: 18479916
DOI: 10.1016/j.bmcl.2008.04.047

Experimental method

X-RAY DIFFRACTION (2.3 Å)