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

文献类型：期刊论文

作者Wang, Yuwei1,2; Tang, Shuai3; Lai, Huanling1; Jin, Ruyi2; Long, Xu2; Li, Na2; Tang, Yuping2; Guo, Hui2; Yao, Xiaojun1; Leung, Elaine Lai-Han1
刊名FRONTIERS IN PHARMACOLOGY
出版日期2020-11-11
卷号11页码:11
ISSN号1663-9812
关键词IDH1 gliomas molecular docking virtual screening docking-based virtual screening
DOI10.3389/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.
WOS关键词ISOCITRATE DEHYDROGENASE 1 ; MUTANT IDH1 ; COMPETITIVE INHIBITOR ; MUTATIONS ; IDENTIFICATION ; DOCKING ; DIFFERENTIATION ; CANCER
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研究方向Pharmacology & Pharmacy
语种英语
出版者FRONTIERS MEDIA SA
WOS记录号WOS:000591901900001
源URL[http://119.78.100.183/handle/2S10ELR8/292623]  
专题新药研究国家重点实验室
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.

入库方式： OAI收割

来源：上海药物研究所

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