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Design, synthesis and evaluation of a novel BRD4 protein inhibitors
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Jian-ping HU1, 2, Yan-lian LI1, 2, Huan-yu SHI1, 2, Bing XIONG1, 2, *, Jing-kang SHEN1, 2
Acta Pharmaceutica Sinica | 2017, 52(10) : 1568 - 1577
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Acta Pharmaceutica Sinica | 2017, 52(10): 1568-1577
• ORIGINAL ARTICLES •
Design, synthesis and evaluation of a novel BRD4 protein inhibitors
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Jian-ping HU1, 2, Yan-lian LI1, 2, Huan-yu SHI1, 2, Bing XIONG1, 2, *, Jing-kang SHEN1, 2
Affiliations
  • 1. Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
  • 2. University of Chinese Academy of Sciences, Beijing 100049, China
Published: 2017-10-12 doi: 10.16438/j.0513-4870.2017-0407
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Bromodomain-containing proteins (BCPs) can specifically recognize acetylated lysine (KAc) in histones and other substrate proteins. Recently, several kinase inhibitors were found to inhibit bromodomains, such as the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which bind to BRD4 with IC50 values of 25 nmol·L-1 and 130 nmol·L-1, respectively. To obtain potent BRD4 inhibitors from inhibitor BI-2536, we used dihydroquinoxalin-2(1H)-one to replace the 7, 8-dihydropteridin-6(5H)-one in BI2536. By exploring the structure-activity relationships of the new dihydroquinoxalin-2(1H)-one structures, we obtained a novel phenyl side chain series of BRD4 inhibitors. We identified several potent BRD4 inhibitors, especially compounds 16, 22, 28 and 29, which had IC50 values below 100 nmol·L-1 in fluorescence anisotropy (FA) assays, indicating this series of compounds are worth to fruther investigation.

BRD4  /  dihydroquinoxalin-2(1H)-one  /  phenyl side chain
Jian-ping HU, Yan-lian LI, Huan-yu SHI, Bing XIONG, Jing-kang SHEN. Design, synthesis and evaluation of a novel BRD4 protein inhibitors[J]. Acta Pharmaceutica Sinica, 2017 , 52 (10) : 1568 -1577 . DOI: 10.16438/j.0513-4870.2017-0407
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Article Info
doi: 10.16438/j.0513-4870.2017-0407
  • Receive Date：2017-04-26
  • Online Date：2026-01-14
  • Published：2017-10-12
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  • Received：2017-04-26
  • Revised：2017-05-02
Affiliations
    1. Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
    2. University of Chinese Academy of Sciences, Beijing 100049, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
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Percentage of total
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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