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. DAF-12 is an orphan nuclear hormone receptor that regulates dauer larva diapause, reproductive development, fat metabolism, and life cycle/longevity in C. elegans. 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. Δ4-Dafachronic acid is a racemic version of a sterol-derived hormone that acts as a ligand of DAF-12. Δ4-Dafachronic acid binds to and transactivates DAF-12, rescuing hormone deficiency in transgenic dauer larvae and promoting reproductive maturation into adults. The (25S) diastereomer of Δ4-dafachronic acid is significantly more potent than its (25R) counterpart (EC50s = 23 and 66 nM, respectively).
