(25S)-d7-Dafachronic Acid

During unfavorable environmental conditions, C. elegans larvae undergo arrest and form dauer larvae that can attach to other animals as a parasitic strategy for survival.{22033,22027} DAF-12 is an orphan nuclear hormone receptor that regulates dauer larva diapause, reproductive development, fat metabolism, and life cycle/longevity in C. elegans.{22030,22029,22015} DAF-12 is required for entry into dauer when it is not bound to ligand by acting as a transcriptional repressor of target genes that favor reproductive development. (25S)-d7-Dafachronic acid is a sterol-derived hormone that acts as a ligand of DAF-12 with an EC50 value of 23 nM.{22030,22032,22014,22028} At 50 nM, (25S)-d7-Dafachronic acid inhibits the dauer-promoting activity of DAF-12, blocking the formation of infective larvae in several parasitic nematodes in favor of reproductive maturation to adults.{22031,22033} Thus, selective ligand modulators of DAF-12 are a potential therapeutic approach to stop larvae progression during parasitic infection.{22027}