期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 27, 期 20, 页码 4606-4613出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2017.09.025
关键词
Epigenetic readers; Bromodomains; BET; BRD4; Triazoloquinoxaline; [1,2,4]Triazolo[4,3-a]quinoxaline; Cancer
资金
- National Research Foundation - Korean government [NRF-2012M3A9C1053340]
- Korea Research Institute of Chemical Technology [KK1703-B01]
- Korea Chemical Bank [SI1707-04]
- National Research Foundation of Korea [2012M3A9C1053340] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3-a]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay. The substantial antiproliferative activities in human cancer cell lines, promising drug-like properties, and the selectivity for the BET family make the lead compound (13) as a novel BRD4 inhibitor motif for anti-cancer drug discovery. (C) 2017 Elsevier Ltd. All rights reserved.
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