Δ4-Dafachronic Acid

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Background

Δ4-Dafachronic acid is a DAF-12 activator.
Steroid hormone dafachronic acid (DA) has been identified to regulate dauer formation and lifespan in Caenorhabditis elegans via binding to the nuclear receptor DAF-12. DAF-12, an orphan nuclear hormone receptor, regulates dauer larva diapause, reproductive development, fat metabolism, as well as life cycle/longevity in C. elegans. In addition, DAF-12 is needed for entry into dauer by acting as a transcriptional repressor of target genes that favor reproductive development when it is not bound to ligand.
In vitro: Δ4-Dafachronic acid is a racemic version of a sterol-derived hormone acting as a ligand of DAF-12. In a previous study, it was found that there was no significant increase in the Δ4- and Δ4-dafachronic acid concentration in the long-lived glp-1 mutant, nor in the mutants defective in dauer formation [1]. Another previous study provided insights into the molecular interface between DA and IIS pathways and suggested that Δ4- and Δ7-dafachronic acid pathways had unique as well as overlapping biological functions in the control of development and lifespan [2].
In vivo: Up to now, there is no animal in vivo study reported for Δ4-Dafachronic acid.
Clinical trial: So far, no clinical study has been conducted.

[1] Li TM et al. No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation. G3 (Bethesda). 2015 May 12;5(7):1473-9.
[2] Dumas, K. J.,Guo, C.,Wang, X., et al. Functional divergence of dafachronic acid pathways in the control of C. elegans development and lifespan. Dev.Biol. 340(2), 605-612 (2010).