Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening

被引：0
|
作者：
Ma, Yanyu [1 ]
Song, Yidan [1 ]
Wang, Junyi [1 ]
Shi, Xiayu [1 ]
Yuan, Zhen [1 ]
Li, Shuang [1 ]
Li, Honglin [1 ,2 ,3 ]
Chen, Zhuo [1 ]
Li, Shiliang [1 ,2 ]
机构：
[1] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, Shanghai, Peoples R China
[2] East China Normal Univ, Innovat Ctr AI & Drug Discovery, Shanghai 200062, Peoples R China
[3] Lingang Lab, Shanghai 200031, Peoples R China
来源：
FUTURE MEDICINAL CHEMISTRY | 2024年 / 16卷 / 07期
基金：
中国国家自然科学基金;
关键词：
cancer treatment; covalent inhibitor; DJ-1; molecular docking; virtual screening; THERAPEUTIC TARGET; ANDROGEN RECEPTOR; CRYSTAL-STRUCTURE; PROTEIN; EXPRESSION; APOPTOSIS; DOCKING; BINDING; CANCER;
D O I：
10.4155/fmc-2023-0301
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Background: DJ-1 is a ubiquitously expressed protein with multiple functions. Its overexpression has been associated with the occurrence of several cancers, positioning DJ-1 as a promising therapeutic target for cancer treatment. Methods: To find novel inhibitors of DJ-1, we employed a hybrid virtual screening strategy that combines structure-based and ligand-based virtual screening on a comprehensive compound library. Results: In silico study identified six hit compounds as potential DJ-1 inhibitors that were assessed in vitro at the cellular level. Compound 797780-71-3 exhibited antiproliferation activity in ACHN cells with an IC50 value of 12.18 mu M and was able to inhibit the Wnt signaling pathway. This study discovers a novel covalent inhibitor for DJ-1 and paves the way for further optimization.
引用
收藏
页码：665 / 677
页数：14
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