3cth

From Proteopedia

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Template:STRUCTURE 3cth

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known disease associated with this structure: Hepatocellular carcinoma, childhood type OMIM:[164860], Renal cell carcinoma, papillary, familial and sporadic OMIM:[164860], Autism, suseptibility to, 9 OMIM:[164860]

About this Structure

3CTH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors., Cai ZW, Wei D, Schroeder GM, Cornelius LA, Kim K, Chen XT, Schmidt RJ, Williams DK, Tokarski JS, An Y, Sack JS, Manne V, Kamath A, Zhang Y, Marathe P, Hunt JT, Lombardo LJ, Fargnoli J, Borzilleri RM, Bioorg Med Chem Lett. 2008 Jun 1;18(11):3224-9. Epub 2008 Apr 25. PMID:18479916 Page seeded by OCA on Wed Jun 11 10:50:19 2008