文献类型：期刊文献

英文题名：Identification of Potent Leucine-Rich Repeat Kinase 2 Inhibitors by Virtual Screening and Biological Evaluation

作者：Shen, Hualiang[1,2];Yu, Guoqi[3];Cai, Tao[1,2];Hu, Kai[2];Shang, Tianbo[1,2];Luo, Yanjuan[1,2];Zhu, Jiawei[4];Bai, Xiaoxue[4];Xiong, Yicheng[4];Xi, Meiyang[1,2];Shen, Runpu[1,2]

机构：[1]Shaoxing Univ, Zhejiang Engn Res Ctr Fat Soluble Vitamin, Shaoxing, Peoples R China;[2]Shaoxing Univ, Sch Chem & Chem Engn, Shaoxing, Peoples R China;[3]Shaoxing Univ, Sch Med, Shaoxing, Peoples R China;[4]China Pharmaceut Univ, Dept Med Chem, Nanjing, Peoples R China

年份：2025

卷号：105

期号：3

起止页码：e70082

外文期刊名：CHEMICAL BIOLOGY & DRUG DESIGN

收录：SCI-EXPANDED(收录号：WOS:001438586600001)、、Scopus(收录号：2-s2.0-86000573970)、WOS

基金：The authors greatly acknowledge the support from the National Natural Science Foundation of China (No. 22278270).

语种：英文

外文关键词：docking; inhibitory activity; leucine-rich repeat kinase 2 (LRRK2); molecular dynamics (MD) simulations; virtual screening (VS)

外文摘要：Parkinson's disease (PD) is the second most common neurodegenerative disease but has limited medications. Targeting leucine-rich repeat kinase 2 (LRRK2) has been identified as a potential strategy for the treatment of PD. The development of LRRK2 inhibitors has attracted much interest, and various compounds have been reported with significant improvement in preclinical and clinical models. Currently, no LRRK2 inhibitor has been approved for PD intervention. Herein, we reported a virtual screening (VS) workflow combining molecular docking and molecular dynamics (MD) simulations to achieve eight compounds for further enzymatic assay. The results indicated a potent LRRK2 inhibitor 2 with IC50 values of 2.396 and 5.996 mu M against LRRK2 and LRRK2 G2019S, respectively, implying the reliability of this VS approach. Combined with predicted favorable drug-like properties, this hit can be used as a starting point for further structural optimization, probably offering insight into targeting LRRK2 for PD treatment in the future.