5UG8

Crystal structure of the EGFR kinase domain (L858R, T790M, V948R) in complex with a covalent inhibitor N-[(3R,4R)-4-fluoro-1-{6-[(1-methyl-1H-pyrazol-4-yl)amino]-9-(propan-2-yl)-9H-purin-2-yl}pyrrolidin-3-yl]propanamide

5UG8 の概要

• エントリーDOI: 10.2210/pdb5ug8/pdb
• 関連するPDBエントリー: 5UG9 5UGA 5UGB 5UGC
• 分子名称: Epidermal growth factor receptor, N-[(3R,4R)-4-fluoro-1-{6-[(1-methyl-1H-pyrazol-4-yl)amino]-9-(propan-2-yl)-9H-purin-2-yl}pyrrolidin-3-yl]propanamide, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: kinase, covalent inhibitor, lung cancer, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38556.42

構造登録者

Gajiwala, K.S.,Ferre, R.A. (登録日: 2017-01-07, 公開日: 2017-03-22, 最終更新日: 2017-04-26)

• 主引用文献: Planken, S.,Behenna, D.C.,Nair, S.K.,Johnson, T.O.,Nagata, A.,Almaden, C.,Bailey, S.,Ballard, T.E.,Bernier, L.,Cheng, H.,Cho-Schultz, S.,Dalvie, D.,Deal, J.G.,Dinh, D.M.,Edwards, M.P.,Ferre, R.A.,Gajiwala, K.S.,Hemkens, M.,Kania, R.S.,Kath, J.C.,Matthews, J.,Murray, B.W.,Niessen, S.,Orr, S.T.,Pairish, M.,Sach, N.W.,Shen, H.,Shi, M.,Solowiej, J.,Tran, K.,Tseng, E.,Vicini, P.,Wang, Y.,Weinrich, S.L.,Zhou, R.,Zientek, M.,Liu, L.,Luo, Y.,Xin, S.,Zhang, C.,Lafontaine, J.; Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR.; J. Med. Chem., 60:3002-3019, 2017; PubMed: 28287730; DOI: 10.1021/acs.jmedchem.6b01894

実験手法

X-RAY DIFFRACTION (1.46 Å)