4ZAU

AZD9291 complex with wild type EGFR

4ZAU の概要

• エントリーDOI: 10.2210/pdb4zau/pdb
• 関連するPDBエントリー: 4WRG
• 分子名称: Epidermal growth factor receptor, N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide (3 entities in total)
• 機能のキーワード: transferase, kinase domain, 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: 38063.06

構造登録者

Squire, C.J.,Yosaatmadja, Y.,Flanagan, J.U.,McKeage, M. (登録日: 2015-04-14, 公開日: 2015-11-11, 最終更新日: 2023-09-27)

主引用文献

Yosaatmadja, Y.,Silva, S.,Dickson, J.M.,Patterson, A.V.,Smaill, J.B.,Flanagan, J.U.,McKeage, M.J.,Squire, C.J.
Binding mode of the breakthrough inhibitor AZD9291 to epidermal growth factor receptor revealed.
J.Struct.Biol., 192:539-544, 2015

PubMed Abstract: The discovery of genetic drivers of lung cancer in patient sub-groups has led to their use as predictive biomarkers and as targets for selective drug therapy. Some of the most important lung cancer drivers are mutations in the EGFR gene, for example, the exon 19 deletions and the L858R variant that confer sensitivity to the front line drugs erlotinib and gefitinib; the acquired T790M variants confer drug resistance and a poor prognosis. A challenge then in targeting EGFR is to produce drugs that inhibit both sensitising variants and resistance variants, leaving wild type protein in healthy cells unaffected. One such agent is AstraZeneca's "breakthrough" AZD9291 molecule that shows a 200-fold selectivity for T790M/L858R over wild type EGFR. Our X-ray crystal structure reveals the binding mode of AZD9291 to the kinase domain of wild type EGFR.

PubMed: 26522274
DOI: 10.1016/j.jsb.2015.10.018

実験手法

X-RAY DIFFRACTION (2.8 Å)