Discovery of new small molecule inhibitors of the BPTF bromodomain

doi:10.1016/j.bioorg.2023.106453

	Discovery of new small molecule inhibitors of the BPTF bromodomain
	Liang, Xiaochen 1,3,5; Cao, Yu 2,3; Duan, Zhe 3; Wang, Mingchen 3; Zhang, Naixia 3; Ding, Yiluan 3; Luo, Cheng 2,3,4,5,6; Lu, Na 1; Chen, Shijie 3,5
	2023-05-01
发表期刊	BIOORGANIC CHEMISTRY; (IF:4.5[JCR-2023],4.7[5-Year])
ISSN	0045-2068
EISSN	1090-2120
卷号	134
发表状态	已发表
DOI	10.1016/j.bioorg.2023.106453
摘要	Chromatin remodeling regulates many basic cellular processes, such as gene transcription, DNA repair, and programmed cell death. As the largest member of nucleosome remodeling factor (NURF), BPTF plays a vital role in the occurrence and development of cancer. Currently, BPTF bromodomain inhibitors are still in development. In this study, by conducting homogenous time-resolved fluorescence resonance energy transfer (HTRF) assay, we identified a potential, novel BPTF inhibitor scaffold Sanguinarine chloride with the IC50 value of 344.2 ± 25.1 nM. Biochemical analysis revealed that compound Sanguinarine chloride exhibited high binding affinity to the BPTF bromodomain. Molecular docking predicted the binding mode of Sanguinarine chloride and elucidated the activities of its derivatives. Moreover, Sanguinarine chloride showed a potent anti-proliferative effect in MIAPaCa-2 cells and inhibited the expression of BPTF target gene c-Myc. Taken together, Sanguinarine chloride provides a qualified chemical tool for developing potent BPTF bromodomain inhibitors.
关键词	BPTF bromodomain BPTF inhibitors c-Myc HTRF
学科门类	Biochemistry ; Molecular Biology ; Drug Discovery ; Organic Chemistry
URL	查看原文
收录类别	SCOPUS ; SCI
语种	英语
资助项目	Youth Innovation Promotion Association of CAS[2022279] ; Science and Technology Commission of Shanghai Municipality[21ZR1474700] ; National Natural Science Foundation of China["81821005","91853205","21820102008"]
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Organic
WOS记录号	WOS:000954529700001
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
原始文献类型	Article
Scopus 记录号	2-s2.0-85149642302
来源库	SCOPUS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/286508
专题	生命科学与技术学院
通讯作者	Lu, Na; Chen, Shijie
作者单位	1.China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Jiangsu Key Lab Carcinogenesis & Intervent,Sch Bas, Nanjing 210009, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Chem Biol, State Key Lab Drug Res,Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式 GB/T 7714	Liang, Xiaochen,Cao, Yu,Duan, Zhe,et al. Discovery of new small molecule inhibitors of the BPTF bromodomain[J]. BIOORGANIC CHEMISTRY;,2023,134.
APA	Liang, Xiaochen.,Cao, Yu.,Duan, Zhe.,Wang, Mingchen.,Zhang, Naixia.,...&Chen, Shijie.(2023).Discovery of new small molecule inhibitors of the BPTF bromodomain.BIOORGANIC CHEMISTRY;,134.
MLA	Liang, Xiaochen,et al."Discovery of new small molecule inhibitors of the BPTF bromodomain".BIOORGANIC CHEMISTRY; 134(2023).