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Dafadine A is a selective inhibitor of C. elegans DAF-9 cytochrome P450, a key regulator of dauer formation, developmental timing and longevity. C. elegans has four life stages. In harsh environmental conditions, nematodes can convert to the L3 stage, known as the ""non-aging"" dauer stage, in which development ceases until improved conditions are sensed. Dafadine A can induce dauer formation and increased longevity in wild-type worms raised in nonstressful conditions. Dafadine A is the only inhibitor known to robustly inhibit DAF-9 in wild-type worms. It does not inhibit DAF-12 activity. Dafadine is active in mammalian systems, inhibiting CYP27A1, the mammalian functional ortholog of DAF-9 that oxidizes 4-cholesten-3-one to make 26-hydroxy-4-cholesten-3-one and Δ4-dafachronic acid, without inhibiting other sterol- and oxysterol-metabolizing P450s such as CYP7A1 or CYP7B1.
Dafadine A is a selective inhibitor of C. elegans DAF-9 cytochrome P450 and CYP7A1, the mammalian ortholog.
