Description
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. (25S)-
Δ
7-
Dafachronic acid is a sterol-
derived hormone that acts as a ligand of DAF-
12 with an EC
50 value of 23 nM. At 50 nM, (25S)-
Δ
7-
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. Thus, selective ligand modulators of DAF-
12 are a potential therapeutic approach to stop larvae progression during parasitic infection.
