{"title":"Advanced technologies for screening and identifying covalent inhibitors","authors":"Yaolin Guo , Wen shuai , Aiping Tong , Yuxi Wang","doi":"10.1016/j.trac.2024.117833","DOIUrl":null,"url":null,"abstract":"<div><p>Covalent inhibitors, forming reversible or irreversible covalent bonds with nucleophilic groups in target protein active sites, effectively inhibit protein function for therapeutic purposes. They can also be used for target validation, biomarker identification, and as chemical probes. Boasting high bioefficiency, low drug resistance, and minimal off-target effects, covalent inhibitors possess significant application potential within the small molecule drug market. Their discovery usually involves rational drug design. Understanding screening and identification tools for covalent inhibitors aids in selecting suitable and efficient development methods. This review encompasses screening platforms, target-ligand covalent binding, and selective analysis tools used in covalent inhibitor development. It focuses on discovery strategies such as computer-aided drug design, library screening, and classic techniques for binding determination and selectivity. Examples highlight the advantages and limitations of screening platforms, offering insights for covalent inhibitor discovery and advancing drug development.</p></div>","PeriodicalId":439,"journal":{"name":"Trends in Analytical Chemistry","volume":null,"pages":null},"PeriodicalIF":11.8000,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Analytical Chemistry","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165993624003169","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Covalent inhibitors, forming reversible or irreversible covalent bonds with nucleophilic groups in target protein active sites, effectively inhibit protein function for therapeutic purposes. They can also be used for target validation, biomarker identification, and as chemical probes. Boasting high bioefficiency, low drug resistance, and minimal off-target effects, covalent inhibitors possess significant application potential within the small molecule drug market. Their discovery usually involves rational drug design. Understanding screening and identification tools for covalent inhibitors aids in selecting suitable and efficient development methods. This review encompasses screening platforms, target-ligand covalent binding, and selective analysis tools used in covalent inhibitor development. It focuses on discovery strategies such as computer-aided drug design, library screening, and classic techniques for binding determination and selectivity. Examples highlight the advantages and limitations of screening platforms, offering insights for covalent inhibitor discovery and advancing drug development.
期刊介绍:
TrAC publishes succinct and critical overviews of recent advancements in analytical chemistry, designed to assist analytical chemists and other users of analytical techniques. These reviews offer excellent, up-to-date, and timely coverage of various topics within analytical chemistry. Encompassing areas such as analytical instrumentation, biomedical analysis, biomolecular analysis, biosensors, chemical analysis, chemometrics, clinical chemistry, drug discovery, environmental analysis and monitoring, food analysis, forensic science, laboratory automation, materials science, metabolomics, pesticide-residue analysis, pharmaceutical analysis, proteomics, surface science, and water analysis and monitoring, these critical reviews provide comprehensive insights for practitioners in the field.