The Power of Sophisticated Phenotypic Screening and Modern Mechanism-of-Action Methods.

Cell Chem Biol
Authors
Keywords
Abstract

The enthusiasm for phenotypic screening as an approach for small-molecule discovery has increased dramatically over the last several years. The recent increase in phenotype-based discoveries is in part due to advancements in phenotypic readouts in improved disease models that recapitulate clinically relevant biology in cell culture. Of course, a major historical barrier to using phenotypic assays in chemical biology has been the challenge in determining the mechanism of action (MoA) for compounds of interest. With the combination of medically inspired phenotypic screening and the development of modern MoA methods, we can now start implementing this approach in chemical probe and drug discovery. In this Perspective, we highlight recent advances in phenotypic readouts and MoA determination by discussing several case studies in which both activities were required for understanding the chemical biology involved and, in some cases, advancing toward clinical development.

Year of Publication
2016
Journal
Cell Chem Biol
Volume
23
Issue
1
Pages
3-9
Date Published
2016 Jan 21
ISSN
2451-9456
DOI
10.1016/j.chembiol.2015.11.008
PubMed ID
26933731
PubMed Central ID
PMC4779180
Links
Grant list
Howard Hughes Medical Institute / United States
R01 GM038627 / GM / NIGMS NIH HHS / United States