Barbara Bosch, Michael A. DeJesus, Dirk Schnappinger, Jeremy M. Rock
{"title":"Weak links: Advancing target-based drug discovery by identifying the most vulnerable targets","authors":"Barbara Bosch, Michael A. DeJesus, Dirk Schnappinger, Jeremy M. Rock","doi":"10.1111/nyas.15139","DOIUrl":null,"url":null,"abstract":"<p><i>Mycobacterium tuberculosis</i> remains the most common infectious killer worldwide despite decades of antitubercular drug development. Effectively controlling the tuberculosis (TB) pandemic will require innovation in drug discovery. In this review, we provide a brief overview of the two main approaches to discovering new TB drugs—phenotypic screens and target-based drug discovery—and outline some of the limitations of each method. We then explore recent advances in genetic tools that aim to overcome some of these limitations. In particular, we highlight a novel metric to prioritize essential targets, termed vulnerability. Stratifying targets based on their vulnerability presents new opportunities for future target-based drug discovery campaigns.</p>","PeriodicalId":8250,"journal":{"name":"Annals of the New York Academy of Sciences","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/nyas.15139","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the New York Academy of Sciences","FirstCategoryId":"103","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/nyas.15139","RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Mycobacterium tuberculosis remains the most common infectious killer worldwide despite decades of antitubercular drug development. Effectively controlling the tuberculosis (TB) pandemic will require innovation in drug discovery. In this review, we provide a brief overview of the two main approaches to discovering new TB drugs—phenotypic screens and target-based drug discovery—and outline some of the limitations of each method. We then explore recent advances in genetic tools that aim to overcome some of these limitations. In particular, we highlight a novel metric to prioritize essential targets, termed vulnerability. Stratifying targets based on their vulnerability presents new opportunities for future target-based drug discovery campaigns.
期刊介绍:
Published on behalf of the New York Academy of Sciences, Annals of the New York Academy of Sciences provides multidisciplinary perspectives on research of current scientific interest with far-reaching implications for the wider scientific community and society at large. Each special issue assembles the best thinking of key contributors to a field of investigation at a time when emerging developments offer the promise of new insight. Individually themed, Annals special issues stimulate new ways to think about science by providing a neutral forum for discourse—within and across many institutions and fields.