Identifying New Ligands for JNK3 by Fluorescence Thermal Shift Assays and Native Mass Spectrometry

doi:10.1021/acsomega.2c00340

	Identifying New Ligands for JNK3 by Fluorescence Thermal Shift Assays and Native Mass Spectrometry
	Cheng, Chongyun 1,2,3; Liu, Miaomiao 2; Gao, Xiaoqin 4; Wu, Dong5 ; Pu, Mengchen 1; Ma, Jun 2; Quinn, Ronald J.2; Xiao, Zhicheng 3,6; Liu, Zhijie1,5,6
	2022-04-26
发表期刊	ACS OMEGA (IF:3.7[JCR-2023],4.0[5-Year])
ISSN	2470-1343
卷号	7 期号:16
发表状态	已发表
DOI	10.1021/acsomega.2c00340
摘要	The c-Jun N-terminal kinases (JNKs) are evolutionary highly conserved serine/threonine kinases. Numerous findings suggest that JNK3 is involved in the pathogenesis of neurodegenerative diseases, so the inhibition of JNK3 may be a potential therapeutic intervention. The identification of novel compounds with promising pharmacological properties still represents a challenge. Fluorescence thermal shift screening of a chemically diversified lead-like scaffold library of 2024 pure compounds led to the initial identification of seven JNK3 binding hits, which were classified into four scaffold groups according to their chemical structures. Native mass spectrometry validated the interaction of 4 out of the 7 hits with JNK3. Binding geometries and interactions of the top 2 hits were evaluated by docking into a JNK3 crystal structure. Hit 5 had a Kd of 21 mu M with JNK3 suggested scaffold 5-(phenylamino)-1H-1,2,3-triazole-4-carboxamide as a novel and selective JNK3 binder.
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Health and Medical Research Council of the Australian Government Early Career Fellowship[1054172] ; Australian Research Council["DP130102400","LE120100170"] ; National Natural Science Foundation of China[31330019]
WOS研究方向	Chemistry
WOS类目	Chemistry, Multidisciplinary
WOS记录号	WOS:000812732900001
出版者	AMER CHEMICAL SOC
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/195044
专题	iHuman研究所_PI研究组_陶厚朝组 iHuman研究所
通讯作者	Quinn, Ronald J.; Xiao, Zhicheng; Liu, Zhijie
作者单位	1.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld 4111, Australia 3.Monash Univ, Monash Biomed Discovery Inst, Melbourne, Vic 3800, Australia 4.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China 5.ShanghaiTech Univ, IHuman Inst, Shanghai 201210, Peoples R China 6.Kunming Med Coll, Kunming 650031, Yunnan, Peoples R China
通讯作者单位	iHuman研究所
推荐引用方式 GB/T 7714	Cheng, Chongyun,Liu, Miaomiao,Gao, Xiaoqin,et al. Identifying New Ligands for JNK3 by Fluorescence Thermal Shift Assays and Native Mass Spectrometry[J]. ACS OMEGA,2022,7(16).
APA	Cheng, Chongyun.,Liu, Miaomiao.,Gao, Xiaoqin.,Wu, Dong.,Pu, Mengchen.,...&Liu, Zhijie.(2022).Identifying New Ligands for JNK3 by Fluorescence Thermal Shift Assays and Native Mass Spectrometry.ACS OMEGA,7(16).
MLA	Cheng, Chongyun,et al."Identifying New Ligands for JNK3 by Fluorescence Thermal Shift Assays and Native Mass Spectrometry".ACS OMEGA 7.16(2022).