Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides

Bioorg Med Chem Lett. 2013 Jul 1;23(13):3818-21. doi: 10.1016/j.bmcl.2013.04.083. Epub 2013 May 6.

Abstract

The soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of epoxy-fatty acids, signaling molecules involved in numerous biologies. Toward finding novel inhibitors of sEH, a library of known drugs was tested for inhibition of sEH. We found that fulvestrant, an anticancer agent, is a potent (KI=26 nM) competitive inhibitor of sEH. From this observation, we found that alkyl-sulfoxides represent a new kind of pharmacophore for the inhibition of sEH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Epoxide Hydrolases / metabolism
  • Estradiol / analogs & derivatives*
  • Estradiol / chemistry
  • Estradiol / pharmacology
  • Fulvestrant
  • Humans
  • Molecular Structure
  • Solubility
  • Structure-Activity Relationship
  • Sulfoxides / chemistry
  • Sulfoxides / pharmacology*

Substances

  • Enzyme Inhibitors
  • Sulfoxides
  • Fulvestrant
  • Estradiol
  • Epoxide Hydrolases