8EQ9

Co-crystal structure of PERK with compound 11

これはPDB形式変換不可エントリーです。

8EQ9 の概要

• エントリーDOI: 10.2210/pdb8eq9/pdb
• 分子名称: Eukaryotic translation initiation factor 2-alpha kinase 3, (2R)-N-[(4M)-4-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-3-methylphenyl]-2-(3-fluorophenyl)-2-hydroxyacetamide (3 entities in total)
• 機能のキーワード: kinase, perk, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37221.79

構造登録者

Zhu, G.,Surman, M.D.,Mulvihill, M.J. (登録日: 2022-10-07, 公開日: 2022-11-30, 最終更新日: 2023-10-25)

主引用文献

Stokes, M.E.,Surman, M.D.,Calvo, V.,Surguladze, D.,Li, A.H.,Gasparek, J.,Betzenhauser, M.,Zhu, G.,Du, H.,Rigby, A.C.,Mulvihill, M.J.
Optimization of a Novel Mandelamide-Derived Pyrrolopyrimidine Series of PERK Inhibitors.
Pharmaceutics, 14:-, 2022

PubMed Abstract: The protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of three endoplasmic reticulum (ER) transmembrane sensors of the unfolded protein response (UPR) responsible for regulating protein synthesis and alleviating ER stress. PERK has been implicated in tumorigenesis, cancer cell survival as well metabolic diseases such as diabetes. The structure-based design and optimization of a novel mandelamide-derived pyrrolopyrimidine series of PERK inhibitors as described herein, resulted in the identification of compound , a potent, selective, and orally bioavailable compound suitable for interrogating PERK pathway biology in vitro and in vivo, with pharmacokinetics suitable for once-a-day oral dosing in mice.

PubMed: 36297668
DOI: 10.3390/pharmaceutics14102233

実験手法

X-RAY DIFFRACTION (2.86 Å)