3HP5

Crystal Structure of Human p38alpha complexed with a pyrimidopyridazinone compound

3HP5 の概要

• エントリーDOI: 10.2210/pdb3hp5/pdb
• 関連するPDBエントリー: 3HLL 3HP2
• 分子名称: Mitogen-activated protein kinase 14, 5-(2,6-dichlorophenyl)-2-[(2,4-difluorophenyl)sulfanyl]-6H-pyrimido[1,6-b]pyridazin-6-one, 2-fluoro-4-[4-(4-fluorophenyl)-1H-pyrazol-3-yl]pyridine, ... (4 entities in total)
• 機能のキーワード: two lobes, three ligands, three binding sites, distal and extra sites. peptide flip, atp-binding, kinase, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, transferase
• 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: 42293.93

構造登録者

Shieh, H.-S.,Williams, J.M.,Stegeman, R.A.,Kurumbail, R.G. (登録日: 2009-06-03, 公開日: 2009-09-29, 最終更新日: 2024-02-21)

主引用文献

Selness, S.R.,Devraj, R.V.,Monahan, J.B.,Boehm, T.L.,Walker, J.K.,Devadas, B.,Durley, R.C.,Kurumbail, R.,Shieh, H.,Xing, L.,Hepperle, M.,Rucker, P.V.,Jerome, K.D.,Benson, A.G.,Marrufo, L.D.,Madsen, H.M.,Hitchcock, J.,Owen, T.J.,Christie, L.,Promo, M.A.,Hickory, B.S.,Alvira, E.,Naing, W.,Blevis-Bal, R.
Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase.
Bioorg.Med.Chem.Lett., 19:5851-5856, 2009

PubMed Abstract: The identification and evolution of a series of potent and selective p38 inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high-throughput screening hit were prepared and their SAR explored. Their design was guided by ligand bound co-crystals of p38alpha. These efforts resulted in the identification of 12r and 19 as orally active inhibitors of p38 with significant efficacy in both acute and chronic models of inflammation.

PubMed: 19751974
DOI: 10.1016/j.bmcl.2009.08.082

実験手法

X-RAY DIFFRACTION (2.3 Å)