Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans

Dafadines, identified in a screen for compounds that induce the dauer phenotype in C. elegans , also promote longevity in adult worms, with both phenotypes occurring through inhibition of DAF-9, a cytochrome P450 involved in the insulin signaling pathway. The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans . Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals.