title: Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans.
abstract: 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.
authors: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors: Genna M
authors: GM
authors: Luciani
authors: Lilia
authors: L
authors: Magomedova
authors: Rachel
authors: R
authors: Puckrin
authors: Malene L
authors: ML
authors: Urbanus
authors: Iain M
authors: IM
authors: Wallace
authors: Guri
authors: G
authors: Giaever
authors: Corey
authors: C
authors: Nislow
authors: Carolyn L
authors: CL
authors: Cummins
authors: Peter J
authors: PJ
authors: Roy
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects; D008136:Longevity / Q000187:drug effects*; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C569572:4-(1-((5-((2,6-dimethylphenoxy)methyl)-3-isoxazolyl)carbonyl)-4-piperidinyl)pyridine; D029742:Caenorhabditis elegans Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D010880:Piperidines; D011725:Pyridines; D003577:Cytochrome P-450 Enzyme System; C486228:DAF-9 protein, C elegans