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

IF 6.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Dermot F. McGinnity , Jerome Meneyrol , Christophe Boldron , Craig Johnstone
{"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 ,&nbsp;Jerome Meneyrol ,&nbsp;Christophe Boldron ,&nbsp;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 &lt;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 ,&nbsp;Jerome Meneyrol ,&nbsp;Christophe Boldron ,&nbsp;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 &lt;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}
引用次数: 0

摘要

尽管取得了进展,但小分子药物的发现仍然缓慢而昂贵。利用人工智能(AI)和机器学习(ML)正在进行范式转变;然而,这些技术进步是必要的,但还不够。我们合作组合的绩效指标包括数据周转时间(5天)和候选交付时间(2.9年,而行业为4.0年)。与优化的流程和有效的决策一起,需要提高翻译的预测性。通过下游的体外和体内模型进展更多的化合物将迅速揭示化合物进展的翻译阈值或关键阻滞剂,人类和机器将积极地从这些数据中学习。我们提倡更多以经验为导向的冒险,并转向“每种化合物都有候选药物”战略,该战略旨在在2年内推出候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Drug Discovery Today
Drug Discovery Today 医学-药学
CiteScore
14.80
自引率
2.70%
发文量
293
审稿时长
6 months
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信