1RW8

Crystal Structure of TGF-beta receptor I kinase with ATP site inhibitor

1RW8 の概要

• エントリーDOI: 10.2210/pdb1rw8/pdb
• 分子名称: TGF-beta receptor type I, 3-(4-FLUOROPHENYL)-2-(6-METHYLPYRIDIN-2-YL)-5,6-DIHYDRO-4H-PYRROLO[1,2-B]PYRAZOLE (3 entities in total)
• 機能のキーワード: tgf-beta receptor i, protein kinase, transferase
• 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: 34744.90

構造登録者

Zhang, F.,Sawyer, J.S. (登録日: 2003-12-16, 公開日: 2005-02-01, 最終更新日: 2023-08-23)

主引用文献

Sawyer, J.S.,Beight, D.W.,Britt, K.S.,Anderson, B.D.,Campbell, R.M.,Goodson Jr., T.,Herron, D.K.,Li, H.Y.,McMillen, W.T.,Mort, N.,Parsons, S.,Smith, E.C.,Wagner, J.R.,Yan, L.,Zhang, F.,Yingling, J.M.
Synthesis and activity of new aryl- and heteroaryl-substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain.
Bioorg.Med.Chem.Lett., 14:3581-3584, 2004

PubMed Abstract: We have expanded our previously reported series of pyrazole-based inhibitors of the TGF-beta type I receptor kinase domain (TbetaR-I) to now include new 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole analogues. Limited examination of the SAR of this new series in both enzyme and cell based in vitro assays has revealed selectivity differences with respect to p38 MAP kinase (p38 MAPK) depending on the nature of the 'warhead' group on the dihydropyrrolopyrazole ring. As with our original pyrazole series, phenyl substituents tended to show greater selectivity against p38 MAPK than those comprised of the quinoline-4-yl moiety. We have also achieved co-crystallization and X-ray analysis of compounds 3 and 15, two potent examples of this new series, with the TbetaR-I receptor kinase domain.

PubMed: 15177479
DOI: 10.1016/j.bmcl.2004.04.007

実験手法

X-RAY DIFFRACTION (2.4 Å)