Shabajee Preety, Gaudeau Albane, Legros Céline, Dorval Thierry, Stéphan Jean-Philippe
Pôle d'expertise Criblage pharmacologique, chimiothèque et biobanques, Institut de Recherches Servier, 125, Chemin de Ronde, 78290 Croissy-sur-Seine, France.
Med Sci (Paris). 2021 Mar;37(3):249-257. doi: 10.1051/medsci/2021013. Epub 2021 Mar 19.
The advent of the molecular biology and the completion of the human genome sequencing prompted the pharmaceutical industry to progressively implement target-centric drug discovery strategies. However, concerns regarding the research and development productivity during the last ten years, combined with technological developments in high-content screening, automation, image analysis and artificial intelligence triggered a renewed interest for the phenotypic drug discovery approaches. Target-centric and phenotypic approaches are more and more considered complementary, hence, positioning the target deconvolution on the critical path. This review analyzes the evolution of the target-centric and phenotypic approaches, focusing more specifically on the high-content screening and the target deconvolution technologies currently available.
分子生物学的出现以及人类基因组测序的完成促使制药行业逐步实施以靶点为中心的药物发现策略。然而,过去十年对研发生产力的担忧,再加上高内涵筛选、自动化、图像分析和人工智能等技术的发展,引发了人们对表型药物发现方法的新兴趣。以靶点为中心和表型的方法越来越被认为是互补的,因此,将靶点反卷积置于关键路径上。本综述分析了以靶点为中心和表型方法的演变,更具体地关注当前可用的高内涵筛选和靶点反卷积技术。