1vjy

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spinqualitylabelsall models 1vjy, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of a Naphthyridine Inhibitor of Human TGF-beta Type I Receptor

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.

Disease

Known diseases associated with this structure: Aortic aneurysm, familial thoracic 5 OMIM:[190181], Furlong syndrome OMIM:[190181], Loeys-Dietz syndrome OMIM:[190181]

About this Structure

1VJY is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

Reference

Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors., Gellibert F, Woolven J, Fouchet MH, Mathews N, Goodland H, Lovegrove V, Laroze A, Nguyen VL, Sautet S, Wang R, Janson C, Smith W, Krysa G, Boullay V, De Gouville AC, Huet S, Hartley D, J Med Chem. 2004 Aug 26;47(18):4494-506. PMID:15317461

Page seeded by OCA on Thu Feb 21 15:36:07 2008