7JS8
STRUCTURE OF HUMAN HDAC2 IN COMPLEX WITH AN ETHYL KETONE INHIBITOR CONTAINING A SPIRO-BICYCLIC GROUP (COMPOUND 22)
Summary for 7JS8
| Entry DOI | 10.2210/pdb7js8/pdb |
| Descriptor | Histone deacetylase 2, ZINC ION, SULFATE ION, ... (7 entities in total) |
| Functional Keywords | histone deacetylase, hydrolase, hydrolase-hydrolase inhibitor complex |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 132927.24 |
| Authors | Klein, D.J.,Yu, W. (deposition date: 2020-08-14, release date: 2021-08-11, Last modification date: 2024-05-22) |
| Primary citation | 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 Cited by 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: 33797924DOI: 10.1021/acs.jmedchem.0c02150 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.634 Å) |
Structure validation
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