Azologs of the Fatty Acid Mimetic Drug Cinalukast Enable Light‐Induced PPARα Activation

Abstract

AbstractPhoto‐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.