title: Small molecule selectivity and specificity profiling using functional protein microarrays.
abstract: Small molecules interact with proteins to perturb their functions, a property that has been exploited both for research applications and to produce therapeutic agents for disease treatment. Commonly utilized approaches for identifying the target proteins for a small molecule have limitations in terms of throughput and resource consumption and lack a mechanism to broadly assess the selectivity profile of the small molecule. Here we describe how protein microarray technology can be applied to the study of small molecule-protein interactions using tritiated small molecules. Protein arrays comprising thousands of full-length functional proteins facilitate target identification for those small molecules discovered in cell-based phenotypic assays and both target validation and off-target binding assessment for compounds discovered in target-based screens. The assays are highly reproducible, sensitive, and scalable, and provide an enabling technology for small molecule selectivity profiling in the context of drug development.
authors.affiliation: Life Technologies, Carlsbad, CA, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kraus
authors.forename: Lihao
authors.initials: L
authors.lastname: Meng
authors.forename: Lisa
authors.initials: L
authors.lastname: Freeman-Cook
mesh_terms: D055808:Drug Discovery / Q000379:methods*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D040081:Protein Array Analysis / Q000379:methods*; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D006728:Hormones