4G34

Crystal Structure of GSK6924 Bound to PERK (R587-R1092, delete A660-T867) at 2.70 A Resolution

4G34 の概要

• エントリーDOI: 10.2210/pdb4g34/pdb
• 関連するPDBエントリー: 3QD2 4G31
• 分子名称: Eukaryotic translation initiation factor 2-alpha kinase 3, 1-[5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indol-1-yl]-2-phenylethanone (3 entities in total)
• 機能のキーワード: deletion mutant, catalytic domain, synthetic inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Endoplasmic reticulum membrane; Single-pass type I membrane protein: Q9NZJ5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35182.70

構造登録者

Gampe, R.T.,Axten, J.M. (登録日: 2012-07-13, 公開日: 2012-08-08, 最終更新日: 2023-09-13)

主引用文献

Axten, J.M.,Medina, J.R.,Feng, Y.,Shu, A.,Romeril, S.P.,Grant, S.W.,Li, W.H.,Heerding, D.A.,Minthorn, E.,Mencken, T.,Atkins, C.,Liu, Q.,Rabindran, S.,Kumar, R.,Hong, X.,Goetz, A.,Stanley, T.,Taylor, J.D.,Sigethy, S.D.,Tomberlin, G.H.,Hassell, A.M.,Kahler, K.M.,Shewchuk, L.M.,Gampe, R.T.
Discovery of 7-Methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a Potent and Selective First-in-Class Inhibitor of Protein Kinase R (PKR)-like Endoplasmic Reticulum Kinase (PERK).
J.Med.Chem., 55:7193-7207, 2012

PubMed Abstract: Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states. Evidence that PERK is implicated in tumorigenesis and cancer cell survival stimulated our search for small molecule inhibitors. Through screening and lead optimization using the human PERK crystal structure, we discovered compound 38 (GSK2606414), an orally available, potent, and selective PERK inhibitor. Compound 38 inhibits PERK activation in cells and inhibits the growth of a human tumor xenograft in mice.

PubMed: 22827572
DOI: 10.1021/jm300713s

実験手法

X-RAY DIFFRACTION (2.7 Å)