Discovery of Novel IDH1 Inhibitor Through Comparative Structure-Based Virtual Screening

doi:10.3389/fphar.2020.579768

	Discovery of Novel IDH1 Inhibitor Through Comparative Structure-Based Virtual Screening
	Wang, Yuwei 1,2; Tang, Shuai 3; Lai, Huanling 1; Jin, Ruyi 2; Long, Xu 2; Li, Na 2; Tang, Yuping 2; Guo, Hui 2; Yao, Xiaojun 1; Leung, Elaine Lai-Han 1
刊名	FRONTIERS IN PHARMACOLOGY
	2020-11-11
卷号	11 页码:11
关键词	IDH1 gliomas molecular docking virtual screening docking-based virtual screening
ISSN号	1663-9812
DOI	10.3389/fphar.2020.579768
通讯作者	Guo, Hui(guohui@sntcm.edu.cn) ; Yao, Xiaojun(xjyao@must.edu.mo) ; Leung, Elaine Lai-Han(lhleung@must.edu.mo)
英文摘要	IDH1 mutations occur in about 20-30% of gliomas and are a promising target for the treatment of cancer. In the present study, the performance of aIDH1(R132H) was verified via glide-docking-based virtual screening. On the basis of the two crystal structures (5TQH and 6B0Z) with the best discriminating ability to identify IDH1(R132H) inhibitors from a decoy set, a docking-based virtual screening strategy was employed for identifying new IDH1(R132H) inhibitors. In the end, 57 structurally diverse compounds were reserved and evaluated through experimental tests, and 10 of them showed substantial activity in targeting IDH1(R132H) (IC50 < 50 mu M). Molecular docking technology showed that L806-0255, V015-1671, and AQ-714/41674992 could bind to the binding pocket composed of hydrophobic residues. These findings indicate that L806-0255, V015-1671, and AQ-714/41674992 have the potential as lead compounds for the treatment of IDH1-mutated gliomas through further optimization.
资助项目	National Natural Science Foundation of China[82003653] ; Shaanxi University of Chinese Medicine[2020XG01] ; Subject Innovation Team of Shaanxi University of ChineseMedicine[2019-PY02] ; Macau Science and Technology Development Fund[005/2014/AMJ] ; Macau Science and Technology Development Fund[082/2015/A3] ; Macau Science and Technology Development Fund[046/2016/A2] ; Macau Science and Technology Development Fund[086/2015/A3]
WOS关键词	ISOCITRATE DEHYDROGENASE 1 ; MUTANT IDH1 ; COMPETITIVE INHIBITOR ; MUTATIONS ; IDENTIFICATION ; DOCKING ; DIFFERENTIATION ; CANCER
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000591901900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/292623]
专题	中国科学院上海药物研究所
通讯作者	Guo, Hui; Yao, Xiaojun; Leung, Elaine Lai-Han
作者单位	1.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau, Peoples R China 2.Shaanxi Univ Chinese Med, Coll Pharm, Xian, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang, Yuwei,Tang, Shuai,Lai, Huanling,et al. Discovery of Novel IDH1 Inhibitor Through Comparative Structure-Based Virtual Screening[J]. FRONTIERS IN PHARMACOLOGY,2020,11:11.
APA	Wang, Yuwei.,Tang, Shuai.,Lai, Huanling.,Jin, Ruyi.,Long, Xu.,...&Leung, Elaine Lai-Han.(2020).Discovery of Novel IDH1 Inhibitor Through Comparative Structure-Based Virtual Screening.FRONTIERS IN PHARMACOLOGY,11,11.
MLA	Wang, Yuwei,et al."Discovery of Novel IDH1 Inhibitor Through Comparative Structure-Based Virtual Screening".FRONTIERS IN PHARMACOLOGY 11(2020):11.