1VJY

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

Summary for 1VJY

• Entry DOI: 10.2210/pdb1vjy/pdb
• Descriptor: TGF-beta receptor type I, 2-[5-(6-METHYLPYRIDIN-2-YL)-2,3-DIHYDRO-1H-PYRAZOL-4-YL]-1,5-NAPHTHYRIDINE (3 entities in total)
• Functional Keywords: transferase, protein kinase, inhibitor complex
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P36897
• Total number of polymer chains: 1
• Total formula weight: 35013.33

Authors

Gellibert, F.,Woolven, J.,Fouchet, M.-H.,Mathews, N.,Goodland, H.,Lovegrove, V.,Laroze, A.,Nguyen, V.-L.,Sautet, S.,Wang, R.,Janson, C.,Smith, W.,Krysa, G.,Boullay, V.,de Gouville, A.-C.,Huet, S.,Hartley, D. (deposition date: 2004-04-07, release date: 2004-08-31, Last modification date: 2023-12-27)

Primary citation

Gellibert, F.,Woolven, J.,Fouchet, M.-H.,Mathews, N.,Goodland, H.,Lovegrove, V.,Laroze, A.,Nguyen, V.-L.,Sautet, S.,Wang, R.,Janson, C.,Smith, W.,Krysa, G.,Boullay, V.,De Gouville, A.-C.,Huet, S.,Hartley, D.
Identification of 1,5-Naphthyridine Derivatives as a Novel Series of Potent and Selective TGF-beta Type I Receptor Inhibitors.
J.Med.Chem., 47:4494-4506, 2004

PubMed Abstract: 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.

PubMed: 15317461
DOI: 10.1021/jm0400247

Experimental method

X-RAY DIFFRACTION (2 Å)