Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins
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- 作者：Brigitt Raux ; Yuliia Voitovich ; Carine Derviaux ; Adrien Lugari ; Etienne Rebuffet ; Sabine Milhas ; Stéphane Priet ; Thomas Roux ; Eric Trinquet ; Jean-Claude Guillemot ; Stefan Knapp ; Jean-Michel Brunel ; Alexey Yu. Fedorov ; Yves Collette ; Philippe Roche ; Stéphane Betzi ; Sébastien Combes ; Xavier Morelli
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：February 25, 2016
- 年：2016
- 卷：59
- 期：4
- 页码：1634-1641
- 全文大小：464K
- ISSN：1520-4804
文摘
A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.