Recent discoveries and applications involving small-molecule microarrays

• We review selected recent probe discoveries and novel applications using SMMs.
• SMM screening can use purified protein and proteins from cellular lysates.
• Both strategies have yielded effective probes and inhibitors for a wide variety of targets.
• SMMs enable functional proteomics-biomarker discovery and reactivity profiling.

High-throughput and unbiased binding assays have proven useful in probe discovery for a myriad of biomolecules, including targets of unknown structure or function and historically challenging target classes. Over the past decade, a number of novel formats for executing large-scale binding assays have been developed and used successfully in probe discovery campaigns. Here we review the use of one such format, the small-molecule microarray (SMM), as a tool for discovering protein–small molecule interactions. This review will briefly highlight selected recent probe discoveries using SMMs as well as novel uses of SMMs in profiling applications.