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.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Epoxide Hydrolases / antagonists & inhibitors*
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Epoxide Hydrolases / metabolism
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Estradiol / analogs & derivatives*
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Estradiol / chemistry
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Estradiol / pharmacology
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Fulvestrant
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Humans
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Molecular Structure
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Solubility
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Structure-Activity Relationship
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Sulfoxides / chemistry
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Sulfoxides / pharmacology*
Substances
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Enzyme Inhibitors
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Sulfoxides
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Fulvestrant
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Estradiol
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Epoxide Hydrolases