3NWW

P38 Alpha kinase complexed with a 2-aminothiazol-5-yl-pyrimidine based inhibitor

3NWW の概要

• エントリーDOI: 10.2210/pdb3nww/pdb
• 分子名称: Mitogen-activated protein kinase 14, 1-[2-(2-{[2-(dimethylamino)ethyl]amino}-6-{2-[(1-methylethyl)amino]-1,3-thiazol-5-yl}pyrimidin-4-yl)benzyl]-3-ethylurea (3 entities in total)
• 機能のキーワード: p38 map kinase, serine/threonine-protein kinase, transferase, 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: 1
• 化学式量合計: 42587.65

構造登録者

Sack, J.S. (登録日: 2010-07-12, 公開日: 2010-09-08, 最終更新日: 2024-02-21)

主引用文献

Lin, S.,Wrobleski, S.T.,Hynes, J.,Pitt, S.,Zhang, R.,Fan, Y.,Doweyko, A.M.,Kish, K.F.,Sack, J.S.,Malley, M.F.,Kiefer, S.E.,Newitt, J.A.,McKinnon, M.,Trzaskos, J.,Barrish, J.C.,Dodd, J.H.,Schieven, G.L.,Leftheris, K.
Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38alpha MAP kinase inhibitors.
Bioorg.Med.Chem.Lett., 20:5864-5868, 2010

PubMed Abstract: The design, synthesis, and structure-activity relationships (SAR) of a series of 2-aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a unique nitrogen-sulfur intramolecular nonbonding interaction to stabilize the conformation required for binding to the p38α active site. X-ray crystallographic studies that confirm the proposed binding mode of this class of inhibitors in p38 α and provide evidence for the proposed intramolecular nitrogen-sulfur interaction are discussed.

PubMed: 20732813
DOI: 10.1016/j.bmcl.2010.07.102

実験手法

X-RAY DIFFRACTION (2.09 Å)