Identification of novel inhibitors of histone acetyltransferase hMOF through high throughput screening

doi:10.1016/j.ejmech.2018.08.026

	Identification of novel inhibitors of histone acetyltransferase hMOF through high throughput screening
	Zhang, Rukang 3,4; Wang, Jiang4 ; Zhao, Liang 4; Liu, Shien 2; Du, Daohai 4; Ding, Hong4 ; Chen, Shijie 4; Yue, Liyan 4; Liu, Yu-Chih 1; Zhang, Chenhua 1
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2018-09-05
卷号	157 页码:867-876
关键词	High throughput screening Epigenetics Histone acetyltransferase MOF Inhibitor
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2018.08.026
文献子类	Article
英文摘要	The histone acetyltransferases (HATS) in mammals include GCN5 N-acetyltransferases, the MOZ, YBF2, SAS2, and TIP60 proteins, and the orphan HATs. The males absent on the first (MOF) is mainly related to acetylation of histone H4 Lys16 and has influence on downstream genes expression. However, the only inhibitor MG149 presented low activity against MOF. Besides, there was no high throughput screening platform on MOF, which limited the inhibitor discovery and functional study. In our study, we set up a high throughput screening platform based on amplified luminescent proximity homogeneous assay (ALPHA), which led us to a moderate inhibitor DC_M01. By chemical modification, we found DC_M01_7, which was the analog of DC_M01 with an IC50 value of 6 mu M. DC_M01_7 significantly inhibited HCT116 cells proliferation and could also inhibit histone 4 lysine 16 acetylation in HCT116 cells. To sum up, our work will probably assist the further development of more potent MOF inhibitors and the functional study of hMOF. (C) 2018 Published by Elsevier Masson SAS.
资助项目	Major Project of Chinese National Programs for Fundamental Research and Development[2015CB910304] ; National Natural Science Foundation of China[21472209] ; National Natural Science Foundation of China[81625022] ; National Natural Science Foundation of China[21472208] ; National Natural Science Foundation of China[81430084] ; Chinese Academy of Sciences[XDA12020353]
WOS关键词	GLOBAL GENE-EXPRESSION ; CHROMATIN TRANSCRIPTION ; BIOLOGICAL EVALUATION ; LUNG-CANCER ; PROTEIN ; ACETYLATION ; REPRESSES ; GCN5 ; MOF ; DESIGN
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000447480000060
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279589]
专题	药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室药物发现与设计中心
通讯作者	Liu, Hong; Luo, Cheng
作者单位	1.Shanghai ChemPartner Co Ltd, 5 Bldg,998 Halei Rd, Shanghai 201203, Peoples R China 2.WuXi AppTec, 288 Fute Zhong Rd, Shanghai 200131, Peoples R China; 3.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Zhang, Rukang,Wang, Jiang,Zhao, Liang,et al. Identification of novel inhibitors of histone acetyltransferase hMOF through high throughput screening[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2018,157:867-876.
APA	Zhang, Rukang.,Wang, Jiang.,Zhao, Liang.,Liu, Shien.,Du, Daohai.,...&Luo, Cheng.(2018).Identification of novel inhibitors of histone acetyltransferase hMOF through high throughput screening.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,157,867-876.
MLA	Zhang, Rukang,et al."Identification of novel inhibitors of histone acetyltransferase hMOF through high throughput screening".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 157(2018):867-876.