{"title":"每一种化合物都是候选物:以经验为导向的冒险方法加速小分子药物的发现","authors":"Dermot F. McGinnity , Jerome Meneyrol , Christophe Boldron , Craig Johnstone","doi":"10.1016/j.drudis.2025.104354","DOIUrl":null,"url":null,"abstract":"<div><div>Despite progress, small-molecule drug discovery remains slow and costly. A paradigm shift is underway by leveraging artificial intelligence (AI) and machine learning (ML); however, these technological advances are necessary but not sufficient. Performance indicators from our partnered portfolio include timelines for data turnaround (5-day) and candidate delivery (2.9 versus 4.0 years for industry). Together with optimised processes and effective decision-making, improved translational predictivity is required. Progressing more compounds through downstream <em>in vitro</em> and <em>in vivo</em> models will rapidly reveal translational thresholds or crucial blockers for compound progression, with humans and machines actively learning from such data. We advocate for more experience-led risk-taking and a mindset shift toward an Every Compound a Candidate strategy, which aims to deliver drug candidates in <2 years.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"30 5","pages":"Article 104354"},"PeriodicalIF":6.5000,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Every Compound a Candidate: experience-led risk-taking approaches to accelerate small-molecule drug discovery\",\"authors\":\"Dermot F. McGinnity , Jerome Meneyrol , Christophe Boldron , Craig Johnstone\",\"doi\":\"10.1016/j.drudis.2025.104354\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Despite progress, small-molecule drug discovery remains slow and costly. A paradigm shift is underway by leveraging artificial intelligence (AI) and machine learning (ML); however, these technological advances are necessary but not sufficient. Performance indicators from our partnered portfolio include timelines for data turnaround (5-day) and candidate delivery (2.9 versus 4.0 years for industry). Together with optimised processes and effective decision-making, improved translational predictivity is required. Progressing more compounds through downstream <em>in vitro</em> and <em>in vivo</em> models will rapidly reveal translational thresholds or crucial blockers for compound progression, with humans and machines actively learning from such data. We advocate for more experience-led risk-taking and a mindset shift toward an Every Compound a Candidate strategy, which aims to deliver drug candidates in <2 years.</div></div>\",\"PeriodicalId\":301,\"journal\":{\"name\":\"Drug Discovery Today\",\"volume\":\"30 5\",\"pages\":\"Article 104354\"},\"PeriodicalIF\":6.5000,\"publicationDate\":\"2025-04-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Discovery Today\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1359644625000674\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Discovery Today","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1359644625000674","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Every Compound a Candidate: experience-led risk-taking approaches to accelerate small-molecule drug discovery
Despite progress, small-molecule drug discovery remains slow and costly. A paradigm shift is underway by leveraging artificial intelligence (AI) and machine learning (ML); however, these technological advances are necessary but not sufficient. Performance indicators from our partnered portfolio include timelines for data turnaround (5-day) and candidate delivery (2.9 versus 4.0 years for industry). Together with optimised processes and effective decision-making, improved translational predictivity is required. Progressing more compounds through downstream in vitro and in vivo models will rapidly reveal translational thresholds or crucial blockers for compound progression, with humans and machines actively learning from such data. We advocate for more experience-led risk-taking and a mindset shift toward an Every Compound a Candidate strategy, which aims to deliver drug candidates in <2 years.
期刊介绍:
Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed.
Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.