7JS8

STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BICYCLIC GROUP (COMPOUND 22)

7JS8 の概要

• エントリーDOI: 10.2210/pdb7js8/pdb
• 分子名称: Histone deacetylase 2, ZINC ION, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: histone deacetylase, hydrolase, hydrolase-hydrolase inhibitor complex
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 132927.24

構造登録者

Klein, D.J.,Yu, W. (登録日: 2020-08-14, 公開日: 2021-08-11, 最終更新日: 2024-05-22)

主引用文献

Yu, W.,Liu, J.,Clausen, D.,Yu, Y.,Duffy, J.L.,Wang, M.,Xu, S.,Deng, L.,Suzuki, T.,Chung, C.C.,Myers, R.W.,Klein, D.J.,Fells, J.I.,Holloway, M.K.,Wu, J.,Wu, G.,Howell, B.J.,Barnard, R.J.O.,Kozlowski, J.
Discovery of Ethyl Ketone-Based Highly Selective HDACs 1, 2, 3 Inhibitors for HIV Latency Reactivation with Minimum Cellular Potency Serum Shift and Reduced hERG Activity.
J.Med.Chem., 64:4709-4729, 2021

PubMed Abstract: We describe the discovery of histone deacetylase (HDACs) 1, 2, and 3 inhibitors with ethyl ketone as the zinc-binding group. These HDACs 1, 2, and 3 inhibitors have good enzymatic and cellular activity. Their serum shift in cellular potency has been minimized, and selectivity against hERG has been improved. They are also highly selective over HDACs 6 and 8. These inhibitors contain a variety of substituted heterocycles on the imidazole or oxazole scaffold. Compounds and stand out due to their good potency, high selectivity over HDACs 6 and 8, reduced hERG activity, optimized serum shift in cellular potency, and good rat and dog PK profiles.

PubMed: 33797924
DOI: 10.1021/acs.jmedchem.0c02150

実験手法

X-RAY DIFFRACTION (1.634 Å)