6F5H

Crystal structure of USP7 in complex with a 4-hydroxypiperidine based inhibitor

6F5H の概要

• エントリーDOI: 10.2210/pdb6f5h/pdb
• 関連するPDBエントリー: 5N9R 5N9T
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 7, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: usp7, reversible, inhibitor, selective, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : Q93009
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84327.20

構造登録者

Harrison, T.,Gavory, G.,O'Dowd, C.,Helm, M.,Flasz, J.,Dossang, A.,Hughes, C.,Cassidy, E.,McClelland, K.,Odrzywol, E.,Page, N.,Barker, O.,Miel, H.,Feutron-Burton, S.,Rountree, J.S.S. (登録日: 2017-12-01, 公開日: 2018-04-11, 最終更新日: 2024-05-08)

主引用文献

O'Dowd, C.R.,Helm, M.D.,Rountree, J.S.S.,Flasz, J.T.,Arkoudis, E.,Miel, H.,Hewitt, P.R.,Jordan, L.,Barker, O.,Hughes, C.,Rozycka, E.,Cassidy, E.,McClelland, K.,Odrzywol, E.,Page, N.,Feutren-Burton, S.,Dvorkin, S.,Gavory, G.,Harrison, T.
Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors.
ACS Med Chem Lett, 9:238-243, 2018

PubMed Abstract: Ubiquitin specific protease 7 (USP7, HAUSP) has become an attractive target in drug discovery due to the role it plays in modulating Mdm2 levels and consequently p53. Increasing interest in USP7 is emerging due to its potential involvement in oncogenic pathways as well as possible roles in both metabolic and immune disorders in addition to viral infections. Potent, novel, and selective inhibitors of USP7 have been developed using both rational and structure-guided design enabled by high-resolution cocrystallography. Initial hits were identified via fragment-based screening, scaffold-hopping, and hybridization exercises. Two distinct subseries are described along with associated structure-activity relationship trends, as are initial efforts aimed at developing compounds suitable for experiments. Overall, these discoveries will enable further research into the wider biological role of USP7.

PubMed: 29541367
DOI: 10.1021/acsmedchemlett.7b00512

実験手法

X-RAY DIFFRACTION (2.16 Å)