Discovery of FAM3 A-targeting Small Molecule Agents Using Integrated Virtual Screening and SPR Technology
10.13865/j.cnki.cjbmb.2025.09.1208
- VernacularTitle:基于虚拟筛选与表面等离子体共振技术的FAM3A小分子药物研究
- Author:
Zi-Shuo XU
1
;
Chao SHI
;
Zhang-Xin CHEN
;
Zhe-Yong XUE
;
Li-Xin HUANG
;
Zhen-Zhan CHANG
Author Information
1. 东北林业大学生命科学学院,哈尔滨 150040
- Publication Type:Journal Article
- Keywords:
family with sequence similarity 3 member A(FAM3A);
non-alcoholic fatty liver disease(NAFLD);
type 2 diabetes mellitus(T2DM);
virtual screening;
drug design
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(11):1711-1718
- CountryChina
- Language:Chinese
-
Abstract:
Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.
