Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes.

ABSTRACT: Phenotypic screening is making a comeback in drug discovery as the maturation of chemical proteomics methods has facilitated target identification for bioactive small molecules. A limitation of these approaches is that time-consuming genetic methods or other means are often required to determine the biologically relevant target (or targets) from among multiple protein-compound interactions that are typically detected. Here, we have combined phenotypic screening of a directed small-molecule library with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify carboxylesterase 3 (Ces3, also known as Ces1d) as a primary molecular target of bioactive compounds that promote lipid storage in adipocytes. We f

SUBMITTER: Dominguez E 

PROVIDER: S-EPMC3953460 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature