Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides

Christophe Morisseau; Svitlana Pakhomova; Sung Hee Hwang; Marcia E. Newcomer; Bruce D. Hammock

doi:10.1016/j.bmcl.2013.04.083

Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides

Christophe Morisseau, Svitlana Pakhomova, Sung Hee Hwang, Marcia E. Newcomer, Bruce D. Hammock

Entomology

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12 Scopus citations

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 (K_I = 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.

Original language	English (US)
Pages (from-to)	3818-3821
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2013.04.083
State	Published - Jul 1 2013

Keywords

Competitive inhibition
Epoxy-eicosatrienoic acids
Fulvestrant
Soluble epoxide hydrolase
X-ray structure

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery
Organic Chemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry
Biochemistry

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10.1016/j.bmcl.2013.04.083

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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.",

keywords = "Competitive inhibition, Epoxy-eicosatrienoic acids, Fulvestrant, Soluble epoxide hydrolase, X-ray structure",

author = "Christophe Morisseau and Svitlana Pakhomova and Hwang, {Sung Hee} and Newcomer, {Marcia E.} and Hammock, {Bruce D.}",

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T1 - Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides

AU - Morisseau, Christophe

AU - Pakhomova, Svitlana

AU - Hwang, Sung Hee

AU - Newcomer, Marcia E.

AU - Hammock, Bruce D.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

KW - Competitive inhibition

KW - Epoxy-eicosatrienoic acids

KW - Fulvestrant

KW - Soluble epoxide hydrolase

KW - X-ray structure

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SP - 3818

EP - 3821

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

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ER -

Inhibition of soluble epoxide hydrolase by fulvestrant and sulfoxides

Abstract

Keywords

ASJC Scopus subject areas

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