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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / drug effects*
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Caenorhabditis elegans / growth & development*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / antagonists & inhibitors*
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Caenorhabditis elegans Proteins / metabolism
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Cytochrome P-450 Enzyme Inhibitors*
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Cytochrome P-450 Enzyme System / metabolism
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Isoxazoles / chemistry
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Isoxazoles / pharmacology*
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Larva / drug effects
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Longevity / drug effects*
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Molecular Structure
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Piperidines / chemistry
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Piperidines / pharmacology*
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Pyridines / chemistry
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Pyridines / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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4-(1-((5-((2,6-dimethylphenoxy)methyl)-3-isoxazolyl)carbonyl)-4-piperidinyl)pyridine
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Caenorhabditis elegans Proteins
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Cytochrome P-450 Enzyme Inhibitors
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Enzyme Inhibitors
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Isoxazoles
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Piperidines
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Pyridines
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Cytochrome P-450 Enzyme System
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DAF-9 protein, C elegans
Associated data
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PubChem-Substance/125311228
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PubChem-Substance/125311229
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PubChem-Substance/125311230
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PubChem-Substance/125311232
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PubChem-Substance/125311587