Discovery of CECR2 Bromodomain Inhibitors with High Selectivities over BPTF Bromodomain
作者机构：Biomedical Research Center of South ChinaCollege of Life SciencesFujian Normal UniversityFuzhouFujian350117 China School of PharmacyFudan University826 Zhangheng RoadShanghai201203 China State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadShanghai201203 China University of Chinese Academy of Sciences19 Yuquan RoadBeijing100049 China School of PharmacyNanchang UniversityNanchangJiangxi330006 China Laboratory of Pharmaceutical AnalysisShanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadZhangjiang Hi-Tech ParkShanghai201203 China School of PharmacyFujian Medical UniversityFuzhouFujian350122 China Guizhou University of Traditional Chinese MedicineGuiyangGuizhou550025 China
出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)
年 卷 期：2022年第40卷第17期
页 面：2072-2080页
核心收录：
学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 0703[理学-化学]
基 金：the Science and Technology Commission of Shanghai Municipality(Y811298033 to Q.L.,and 19XD1404700 to C.L.) the scientific research innovation program“Xiyuanjiang River Scholarship”of the College of Life Sciences,Fujian Normal University the State Key Laboratory of Drug Research(SIMM2105KF-07toH.L.) Fujian Provincial Natural Science Foundation(2021J01203 to H.L.) the Natural Science Foundation of Fujian Province(2019J05073 to J.L.) the Joint Funds forthe Innovation of Science and Technology of Fujian Province(2018Y9071 to J.L.)
主 题：CECR2 bromodomain BPTF bromodomain Inhibitors Structure-activity relationships chemical probe
摘 要：Cat s eye syndrome chromosome candidate 2 bromodomain(CECR2 BRD)and Bromodomain PHD transcription factor bromodomain(BPTF BRD)are the same subfamily proteins,both of which are highly conserved in sequence and binding *** remain in the development of small molecules to inhibit one of the two bromodomains(BRDs),in view of each subtype may possess unique physiological and pathological *** is still a lack of effective selective inhibitors of CECR2 BRD,which makes it difficult to fully understand the pathogenesis of CECR2-BRD in diseases,especially ***,we report our efforts to discover a series of highly selective CECR2 BRD inhibitors over BPTF BRD based on ***-based molecular optimization led to the discovery of DC-CEi-26,whose IC_(50) for CECR2 BRD was 96.7±14.9 nmol/L and selectivity was up to 590×over BPTF ***-CEi-26 showed weak potencies for other classic BRDs in different subfamily,which may serve as a chemical probe for CECR2 BRD biological research.
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