Discovery of novel anti-fibrotics through phenotypic screening

Abstract

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.