Profiling Disease-Selective Drug Targets: From Proteomics to Ligandomics

Authors

Prabuddha Waduge
Hong Tian
Keith A Webster
Wei Li

Publication Date

3-1-2023

Journal

Drug Discovery Today

DOI

10.1016/j.drudis.2022.103430

PMID

36343915

PMCID

PMC9974940

PubMedCentral® Posted Date

3-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Proteomics, Drug Delivery Systems, Drug Discovery, ligandomics, comparative ligandomics, drug target discovery, disease-targeted anti-Scg3 therapy, functional proteomics, scRNA-seq

Abstract

Despite advancements in omics technologies, including proteomics and transcriptomics, identification of therapeutic targets remains challenging. Ligandomics recently emerged as a unique technology of functional proteomics for global profiling of cell-binding protein ligands. When applied to diseased versus healthy vasculatures, comparative ligandomics systematically maps novel disease-restricted ligands that allow selective targeting of pathological but not physiological pathways, providing high efficacy with intrinsic safety. In this review, we discuss the potential of cellular ligands as therapeutic targets and summarize the development of ligandomics. We further compare the advantages and limitations of different omics technologies for drug target discovery and discuss target selection criteria to improve drug R&D success rates.