Abstract
Photo-switchable nuclear receptor modulators ("photohormones") enable spatial and temporal control over transcription factor activity and are valuable precision tools for biological studies. We have developed a new photohormone chemotype by incorporating a light-switchable motif in the scaffold of a cinalukast-derived PPARα ligand and tuned light-controlled activity by systematic structural variation. An optimized photohormone exhibited PPARα agonism in its light-induced (Z)-configuration and strong selectivity over related lipid-activated transcription factors representing a valuable addition to the collection of light-controlled tools to study nuclear receptor activity.
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