4E4X

Crystal Structure of B-Raf Kinase Domain in Complex with a Dihydropyrido[2,3-d]pyrimidinone-based Inhibitor

4E4X の概要

• エントリーDOI: 10.2210/pdb4e4x/pdb
• 分子名称: Serine/threonine-protein kinase B-raf, N-(2,4-difluoro-3-{2-[(3-hydroxypropyl)amino]-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl}phenyl)propane-1-sulfonamide (2 entities in total)
• 機能のキーワード: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (By similarity): P15056
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71370.25

構造登録者

Voegtli, W.C.,Sturgis, H.L. (登録日: 2012-03-13, 公開日: 2012-05-09, 最終更新日: 2024-02-28)

主引用文献

Ren, L.,Ahrendt, K.A.,Grina, J.,Laird, E.R.,Buckmelter, A.J.,Hansen, J.D.,Newhouse, B.,Moreno, D.,Wenglowsky, S.,Dinkel, V.,Gloor, S.L.,Hastings, G.,Rana, S.,Rasor, K.,Risom, T.,Sturgis, H.L.,Voegtli, W.C.,Mathieu, S.
The discovery of potent and selective pyridopyrimidin-7-one based inhibitors of B-Raf(V600E) kinase.
Bioorg.Med.Chem.Lett., 22:3387-3391, 2012

PubMed Abstract: Herein we describe the discovery of a novel series of ATP competitive B-Raf inhibitors via structure based drug design (SBDD). These pyridopyrimidin-7-one based inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. Optimization led to the identification of compound 17, a potent, selective and orally available agent with excellent pharmacokinetic properties and robust tumor growth inhibition in xenograft studies.

PubMed: 22534450
DOI: 10.1016/j.bmcl.2012.04.015

実験手法

X-RAY DIFFRACTION (3.6 Å)