3PRF

Crystal Structure of Human B-Raf Kinase Domain in Complex with a Non-Oxime Furopyridine Inhibitor

3PRF の概要

• エントリーDOI: 10.2210/pdb3prf/pdb
• 関連するPDBエントリー: 3PPJ 3PPK 3PRI
• 分子名称: Serine/threonine-protein kinase B-raf, 2-chloro-5-{[2-(pyrimidin-2-yl)furo[2,3-c]pyridin-3-yl]amino}phenol (2 entities in total)
• 機能のキーワード: protein kinase, atp-competitive inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71112.76

構造登録者

Voegtli, W.C.,Vigers, G.P.A.,Morales, T.,Brandhuber, B.J. (登録日: 2010-11-29, 公開日: 2011-02-02, 最終更新日: 2024-02-21)

主引用文献

Ren, L.,Wenglowsky, S.,Miknis, G.,Rast, B.,Buckmelter, A.J.,Ely, R.J.,Schlachter, S.,Laird, E.R.,Randolph, N.,Callejo, M.,Martinson, M.,Galbraith, S.,Brandhuber, B.J.,Vigers, G.,Morales, T.,Voegtli, W.C.,Lyssikatos, J.
Non-oxime inhibitors of B-Raf(V600E) kinase.
Bioorg.Med.Chem.Lett., 21:1243-1247, 2011

PubMed Abstract: The development of inhibitors of B-Raf(V600E) serine-threonine kinase is described. Various head-groups were examined to optimize inhibitor activity and ADME properties. Several of the head-groups explored, including naphthol, phenol and hydroxyamidine, possessed good activity but had poor pharmacokinetic exposure in mice. Exposure was improved by incorporating more metabolically stable groups such as indazole and tricyclic pyrazole, while indazole could also be optimized for good cellular activity.

PubMed: 21251822
DOI: 10.1016/j.bmcl.2010.12.061

実験手法

X-RAY DIFFRACTION (2.9 Å)