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

Nat Chem Biol. 2011 Nov 6;7(12):891-3. doi: 10.1038/nchembio.698.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / antagonists & inhibitors*
  • Caenorhabditis elegans Proteins / metabolism
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology*
  • Larva / drug effects
  • Longevity / drug effects*
  • Molecular Structure
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 4-(1-((5-((2,6-dimethylphenoxy)methyl)-3-isoxazolyl)carbonyl)-4-piperidinyl)pyridine
  • Caenorhabditis elegans Proteins
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Isoxazoles
  • Piperidines
  • Pyridines
  • Cytochrome P-450 Enzyme System
  • DAF-9 protein, C elegans

Associated data

  • PubChem-Substance/125311228
  • PubChem-Substance/125311229
  • PubChem-Substance/125311230
  • PubChem-Substance/125311232
  • PubChem-Substance/125311587