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

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 Descriptor: Epidermal growth factor receptor, GLYCEROL, 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, ... Authors: Gajiwala, K.S, Ferre, R.A. Deposit date: 2017-01-07 Release date: 2017-03-22 Last modified: 2024-11-20 Method: X-RAY DIFFRACTION (1.46 Å) Cite: 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, 2017

携带L858R、T790M、V948R突变的表皮生长因子受体（Epidermal Growth Factor Receptor, EGFR）激酶结构域与共价抑制剂N-[(3R,4R)-4-氟-1-{6-[(1-甲基-1H-吡唑-4-基)氨基]-9-(异丙基)-9H-嘌呤-2-基}吡咯烷-3-基]丙酰胺的共晶结构
描述符：表皮生长因子受体、甘油（GLYCEROL）、N-[(3R,4R)-4-氟-1-{6-[(1-甲基-1H-吡唑-4-基)氨基]-9-(异丙基)-9H-嘌呤-2-基}吡咯烷-3-基]丙酰胺……
作者：Gajiwala K.S、Ferre R.A.
沉积日期：2017-01-07
发布日期：2017-03-22
最后修改日期：2024-11-20
实验方法：X射线衍射（X-ray Diffraction，分辨率1.46 Å）
引用文献：通过基于结构的药物设计发现N-((3R,4R)-4-氟-1-(6-((3-甲氧基-1-甲基-1H-吡唑-4-基)氨基)-9-甲基-9H-嘌呤-2-基)吡咯烷-3-基)丙烯酰胺（PF-06747775）：一种靶向致癌EGFR突变体且对野生型EGFR具有选择性的高亲和力不可逆抑制剂。《药物化学杂志》，60卷，2017年