Drug target discovery for idiopathic pulmonary fibrosis via druggable genome-wide Mendelian randomization
10.7644/j.issn.1674-9960.2025.05.005
- VernacularTitle:基于可成药全基因组孟德尔随机化分析的特发性肺纤维化药物靶点挖掘
- Author:
Xueyang LIN
1
;
Simin LANG
;
Yufeng YANG
;
Chen YANG
;
Ziqi CUI
;
Yuan LUO
;
Yongan WANG
Author Information
1. 青岛大学药学院,山东青岛 266071;军事科学院军事医学研究院,国家安全特需药品全国重点实验室,北京 100850
- Keywords:
idiopathic pulmonary fibrosis;
druggable genes;
two-sample Mendelian randomization;
drug enrichment analysis;
molecular docking
- From:
Military Medical Sciences
2025;49(5):356-363
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis(IPF)and predict therapeutic candidates using a two-sample Mendelian randomization(MR)approach across the druggable genome.Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes.A two-sample MR analysis was performed to infer causal relationships between genes and IPF.Functional enrichment analyses,including Gene Ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG),were conducted to explore biological pathways.Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities.Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF(P＜0.05).Four hub genes(NOD2,LATS2,LTA,and TCF7L2)were enriched in IPF-related pathways,notably Hippo and TNF signaling.Six potential therapeutics were identified:oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1.Molecular docking confirmed strong binding affinities between these drugs and their targets.Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF.The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.
