Lapthorn Alice R, Harding-Fox Sophie L, Feltham Kieran M, Ilg Marcus M, Cellek Selim
Fibrosis Research Group, Medical Technology Research Centre, Anglia Ruskin University, Chelmsford, Essex, UK.
Fibrosis Research Group, Medical Technology Research Centre, Anglia Ruskin University, Chelmsford, Essex, UK.
Drug Discov Today. 2025 Sep;30(9):104450. doi: 10.1016/j.drudis.2025.104450. Epub 2025 Aug 13.
Fibrosis is defined as the excessive accumulation of extracellular matrix (ECM) components following injury, affecting any organ in the human body. Fibrotic diseases of the vital organs (e.g. lung, heart, kidney, and liver) can be chronic, progressive, irreversible, and fatal. Although fibrotic diseases account for 45% of the mortality in the Western world, the available treatment options are limited in number, efficacy, and safety. There is a lack of progress in the development of novel anti-fibrotics, which has been attributed to a reliance on target-based screening. Phenotypic screening has been shown to be more successful in identifying first-in-class drugs compared with the target-based approach. Here we critically review the current landscape of phenotypic screening campaigns in fibrosis, evaluate their success in identifying translatable lead compounds, and highlight methodological pitfalls.
纤维化的定义是损伤后细胞外基质（ECM）成分过度积累，可影响人体的任何器官。重要器官（如肺、心脏、肾脏和肝脏）的纤维化疾病可能是慢性、进行性、不可逆且致命的。尽管纤维化疾病在西方世界的死亡率中占45%，但现有的治疗选择在数量、疗效和安全性方面都很有限。新型抗纤维化药物的开发缺乏进展，这归因于对基于靶点的筛选的依赖。与基于靶点的方法相比，表型筛选已被证明在识别同类首创药物方面更成功。在此，我们批判性地回顾了目前纤维化表型筛选活动的情况，评估它们在识别可转化先导化合物方面的成功，并强调方法上的缺陷。
