Hassell-Hart, Storm, Picaud, Sarah, Lengacher, Raphael, Csucker, Joshua, Millet, Regis, Gasser, Gilles, Alberto, Roger, Maple, Hannah, Felix, Robert, Leśnikowski, Zbigniew J, Stewart, Helen J S, Chevassut, Timothy J, Morley, Simon, Filippakopoulos, Panagis and Spencer, John (2021) Probing BRD inhibition substituent effects in bulky analogues of (+)-JQ1. Helvetica Chimica Acta, 104 (3). a2000214 1-7. ISSN 0018-019X
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Abstract
A series of bulky organometallic and organic analogues of the bromodomain (BRD) inhibitor (+)-JQ1 have been prepared. The most potent, N-[(adamantan-1-yl)methyl]-2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide, 2e, showed excellent potency with an KD=ca. 130 nm vs. BRD4(1) and a ca. 2-fold selectivity over BRD4(2) (KD=ca. 260 nm). Its binding to the first bromodomain of BRD4 was determined by a protein cocrystal structure.
Item Type: | Article |
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Schools and Departments: | Brighton and Sussex Medical School > Clinical and Experimental Medicine School of Life Sciences > Chemistry |
SWORD Depositor: | Mx Elements Account |
Depositing User: | Mx Elements Account |
Date Deposited: | 11 Feb 2021 08:25 |
Last Modified: | 28 Feb 2022 12:15 |
URI: | http://sro.sussex.ac.uk/id/eprint/97083 |
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📧 Request an updateProject Name | Sussex Project Number | Funder | Funder Ref |
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Poised Fragment Libraries for Atypical Bromodomain Inhibition | G2210 | EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCIL | EP/P026990/1 |