In‐Bead Screening of Hydroxamic Acids for the Identification of HDAC Inhibitors

A one bead–one compound screening format is presented. Following solid‐phase synthesis on a photolabile linker, library compounds were readily released and screened inside polymer beads. The release of screening compounds was readily controlled by varying photolysis time and light intensity. Dose‐response experiments were carried out to effectively distinguish high‐ and low‐affinity ligands. A library containing 55 800 compounds was synthesized and screened in a fluorometric assay, thereby identifying potent HDAC inhibitors with IC₅₀ values in the nanomolar range.