1VJY

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

1VJY の概要

• エントリーDOI: 10.2210/pdb1vjy/pdb
• 分子名称: 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)
• 機能のキーワード: transferase, protein kinase, inhibitor complex
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P36897
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35013.33

構造登録者

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. (登録日: 2004-04-07, 公開日: 2004-08-31, 最終更新日: 2023-12-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)