3S3I

p38 kinase crystal structure in complex with small molecule inhibitor

3S3I の概要

• エントリーDOI: 10.2210/pdb3s3i/pdb
• 分子名称: Mitogen-activated protein kinase 14, 3-(3-tert-butyl[1,2,4]triazolo[4,3-a]pyridin-7-yl)-N-cyclopropyl-4-methylbenzamide (3 entities in total)
• 機能のキーワード: p38 map kinase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q16539
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40383.25

構造登録者

Segarra, V.,Aiguade, J.,Roca, R.,Fisher, M.,Lamers, M. (登録日: 2011-05-18, 公開日: 2012-04-04, 最終更新日: 2023-09-13)

主引用文献

Aiguade, J.,Balague, C.,Carranco, I.,Caturla, F.,Dominguez, M.,Eastwood, P.,Esteve, C.,Gonzalez, J.,Lumeras, W.,Orellana, A.,Preciado, S.,Roca, R.,Vidal, L.,Vidal, B.
Novel triazolopyridylbenzamides as potent and selective p38 alpha inhibitors.
Bioorg.Med.Chem.Lett., 22:3431-3436, 2012

PubMed Abstract: A new class of p38α inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38α was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38α inhibitors and ultimately afforded compounds showing good in vivo efficacy.

PubMed: 22521646
DOI: 10.1016/j.bmcl.2012.03.099

実験手法

X-RAY DIFFRACTION (1.8 Å)