Cayman (25S)-Δ7-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.^1,2 DAF-12 is an orphan nuclear hormone receptor that regulates dauer larva diapause, reproductive development, fat metabolism, and life cycle/longevity in C. elegans.^3,4,5 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)-Δ⁷-Dafachronic acid is a sterol-derived hormone that acts as a ligand of DAF-12 with an EC₅₀ value of 23 nM.^3,6,7,8 At 50 nM, (25S)-Δ⁷-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.^9,1 Thus, selective ligand modulators of DAF-12 are a potential therapeutic approach to stop larvae progression during parasitic infection.²

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