title: Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides.
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.
authors.affiliation: Department of Entomology and UCD Comprehensive Cancer Center, University of California, One Shields Avenue, Davis, CA 95616, USA. chmorisseau@ucdavis.edu
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.forename: Svitlana
authors.initials: S
authors.lastname: Pakhomova
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Marcia E
authors.initials: ME
authors.lastname: Newcomer
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077267:Fulvestrant; D006801:Humans; D015394:Molecular Structure; D012995:Solubility; D013329:Structure-Activity Relationship; D013454:Sulfoxides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D013454:Sulfoxides; D000077267:Fulvestrant; D004958:Estradiol; D004851:Epoxide Hydrolases