High content phenotypic and pathway profiling to advance drug discovery in diseases of unmet need

Research output: Contribution to journalArticlepeer-review

Abstract

Conventional thinking in modern drug discovery postulates that the design of highly selective molecules which act on a single disease-associated target will yield safer and more effective drugs. However, high clinical attrition rates and lack of progress in developing new effective treatments for many important diseases of unmet therapeutic need challenge this universal hypothesis. This assumption also impinges upon the efficiency of target agnostic phenotypic
drug discovery strategies, where early target-deconvolution is seen as a critical step to progression of phenotypic hits. In this review we provide an overview of how emerging phenotypic and pathway profiling technologies integrate to deconvolute the mechanism-ofaction of phenotypic hits. We propose that such in-depth mechanistic profiling may support more efficient phenotypic drug discovery strategies which are designed to more appropriately address complex heterogenous diseases of unmet need.
Original languageEnglish
JournalCell Chemical Biology
Early online date18 Mar 2021
DOIs
Publication statusE-pub ahead of print - 18 Mar 2021

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