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Information on EC 3.3.2.10 - soluble epoxide hydrolase and Organism(s) Mus musculus and UniProt Accession P34914
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3.3.2.10 soluble epoxide hydrolaseIUBMB Comments
Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism . It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 3.1.3.76, lipid-phosphate phosphatase [1,2]. Like EC 3.3.2.9, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl---enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) .
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Word Map
- 3.3.2.10
-
epoxyeicosatrienoic
-
arachidonic
- diol
- s-transferase
- hydrolases
- hypertension
-
benzoapyrene
- epoxygenase
- styrene
-
dihydroxyeicosatrienoic
-
enantioselectivity
- phenobarbital
-
dhets
- trans-stilbene
-
leukotriene
-
eicosanoids
-
drug-metabolizing
- cyp1a1
- 3-methylcholanthrene
-
o-deethylase
- oxylipins
-
xenobiotic-metabolizing
-
dihydrodiols
-
enantiopure
-
ethoxyresorufin
- lta4
-
glycidyl
- arene
-
urea-based
- cyclohexene
-
ethoxycoumarin
- medicine
- beta-naphthoflavone
-
oxirane
-
20-hydroxyeicosatetraenoic
-
udp-glucuronyltransferase
- 20-hete
- cyp2j2
-
udp-glucuronosyl
- 1-naphthol
- aminopyrine
-
edhfs
- analysis
- radiobacter
-
3-methylcholanthrene-treated
- butadiene
-
udpgt
-
hydroxyeicosatetraenoic
- epichlorohydrin
- aldrin
- synthesis
-
pentoxyresorufin
- drug development
- agriculture
-
adamantyl
- pharmacology
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
epoxide hydrolase, soluble epoxide hydrolase, ephx2, cytosolic epoxide hydrolase, epoxide hydrolase 1, epoxide hydrolase 2, ephx3, teso hydrolase, hepoxilin hydrolase, bnseh1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
SEH
-
SEH
additional information
SEH
-
-
SEH
-
sEH is a bifunctional enzyme with two catalytic domains: a C-terminal epoxide hydrolase domain and an N-terminal phosphatase domain
additional information
the enzyme belongs to a family of enzymes which catalyze the hydrolysis of epoxyeicosatrienoic acids
additional information
-
the enzyme belongs to the alpha/beta-hydrolase fold family of proteins
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
an epoxide + H2O = a glycol
two step mechanism with formation of of a hydroxyl-alkyl-enzyme intermediate, catalytic triad is Asp333-His523-Asp495 with polarizing residues Tyr381 and Tyr465, catalytic cycle
-
an epoxide + H2O = a glycol
detailed reaction mechanism, molecular dynamics simulations, detailed analysis of substrate binding to the active site and determination of the preferred conformation, involving Tyr381, Tyr465, and His523
an epoxide + H2O = a glycol
the C-terminal part harbors the epoxide hydrolase activity, the phosphatase activity of the enzyme is located at the N-terminal part of EC 3.1.3.76, both catalytic sites act independently
an epoxide + H2O = a glycol
catalytic reaction mechanism involving Tyr465, Tyr381, Asp495, His523, and Asp333, overview
an epoxide + H2O = a glycol
the catalytic mechanism involves two step processes, overview
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
epoxide hydrolase
Catalyses the hydrolysis of trans-substituted epoxides, such as trans-stilbene oxide, as well as various aliphatic epoxides derived from fatty-acid metabolism [7]. It is involved in the metabolism of arachidonic epoxides (epoxyicosatrienoic acids; EETs) and linoleic acid epoxides. The EETs, which are endogenous chemical mediators, act at the vascular, renal and cardiac levels to regulate blood pressure [4,5]. The enzyme from mammals is a bifunctional enzyme: the C-terminal domain exhibits epoxide-hydrolase activity and the N-terminal domain has the activity of EC 3.1.3.76, lipid-phosphate phosphatase [1,2]. Like EC 3.3.2.9, microsomal epoxide hydrolase, it is probable that the reaction involves the formation of an hydroxyalkyl---enzyme intermediate [4,6]. The enzyme can also use leukotriene A4, the substrate of EC 3.3.2.6, leukotriene-A4 hydrolase, but it forms 5,6-dihydroxy-7,9,11,14-icosatetraenoic acid rather than leukotriene B4 as the product [9,10]. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol 5,6-oxide hydrolase) [7].
CAS REGISTRY NUMBER
COMMENTARY
9048-63-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(1S,2S)-trans-methylstyrene oxide + H2O
?
a hydrogen bond from Tyr465 to the substrate oxygen is essential for controlling the regioselectivity of the reaction
-
-
r
(5Z,11Z,14Z)-8,9-epoxyeicosa-5,11,14-trienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosa-5,11,14-trienoic acid
i.e. 8,9-EET
i.e. 8,9-DHET
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
(5Z,8Z,11Z)-14,15-epoxyeicosa-5,8,11-trienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosa-5,8,11-trienoic acid
i.e. 14,15-EET
i.e. 14,15-DHET
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
(5Z,8Z,14Z)-11,12-epoxyeicosa-5,8,14-trienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosa-5,8,14-trienoic acid
i.e. 11,12-EET
i.e. 11,12-DHET
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
(8Z,11Z,14Z)-5,6-epoxyeicosa-8,11,14-trienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosa-8,11,14-trienoic acid
i.e. 5,6-EET
i.e. 5,6-DHET
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
(9Z)-12,13-epoxyoctadecenoic acid + H2O
(9Z)-12,13-dihydroxyoctadecenoic acid
-
-
-
?
11,12-epoxyeicosatrienoic acid + H2O
11,12-dihydroxyeicosatrienoic acid
-
-
-
?
11R,12S-epoxyeicosatrienoic acid + H2O
11R,12S-dihydroxyeicosatrienoic acid
-
-
-
?
11S,12R-epoxyeicosatrienoic acid + H2O
11S,12R-hydroxyeicosatrienoic acid
-
-
-
?
14,15-epoxyeicosatrienoic acid + H2O
14,15-dihydroxyeicosatrienoic acid
-
-
-
?
14R,15S-epoxyeicosatrienoic acid + H2O
14R,15S-dihydroxyeicosatrienoic acid
-
-
-
?
14S,15R-epoxyeicosatrienoic acid + H2O
14S,15R-dihydroxyeicosatrienoic acid
-
-
-
?
14S,15S-trans-epoxy-(5Z,8Z,10E,12E)-eicosatetraenoic acid + H2O
14S,15R-dihydroxy-(5Z,8Z,10E,12E)-eicosatetraenoic acid
-
-
-
?
5,6-epoxyeicosatrienoic acid + H2O
5,6-dihydroxyeicosatrienoic acid
-
-
-
?
8,9-epoxyeicosatrienoic acid + H2O
8,9-dihydroxyeicosatrienoic acid
-
-
-
?
8R,9S-epoxyeicosatrienoic acid + H2O
8R,9S-dihydroxyeicosatrienoic acid
-
-
-
?
8S,9R-epoxyeicosatrienoic acid + H2O
8S,9R-dihydroxyeicosatrienoic acid
-
-
-
?
9(10),12(13)-diepoxyoctadecanoic acid + H2O
9,10,12,13-tetrahydroxyoctadecanoic acid
-
-
-
?
cis-14,15-epoxyeicosatrienoic acid + H2O
cis-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(10R)-hydroxy-(11S,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoic acid + H2O
(10R,11R,12S)-trihydroxy-(5Z,8Z,14Z)-eicosatrienoic acid
-
i.e. hepoxilin B3
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosa-5,11,14-trienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosa-5,11,14-trienoic acid
-
i.e. 8,9-EET
i.e. 8,9-DHET
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosa-5,8,11-trienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosa-5,8,11-trienoic acid
-
i.e. 14,15-EET
i.e. 14,15-DHET
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosa-5,8,14-trienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosa-5,8,14-trienoic acid
-
i.e. 11,12-EET
i.e. 11,12-DHET
-
?
(8R)-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoic acid + H2O
(8R,11R,12S)-trihydroxy-(5Z,9E,14Z)-eicosatrienoic acid
-
i.e. hepoxilin A3, hydrolysis in liver is mainly catalyzed by soluble epoxide hydrolase
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosa-8,11,14-trienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosa-8,11,14-trienoic acid
-
i.e. 5,6-EET
i.e. 5,6-DHET
-
?
1,2,3,4,9,9-hexachloro-6,7-epoxy-1,4,41,5,6,7,8,8a-octahydro-1,4-methanonaphthalene + H2O
?
-
i.e. HEOM
-
-
?
2-methyl styrene oxide + H2O
(2R)-2-phenylpropane-1,2-diol
-
-
highly enantioselective in ionic liquid [bmim][PF6]in presence of 10% water
-
?
4-nitrophenyl (2R,3R)-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate + H2O
?
-
-
-
-
?
4-nitrophenyl (2S,3S)-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate + H2O
?
-
preferred phenylpropyl carbonate substrate
-
-
?
4-t-butylstyrene oxide + H2O
(1R)-1-(4-t-butylphenyl)ethane-1,2-diol
-
-
highly enantioselective in ionic liquid [bmim][PF6]in presence of 10% water
-
?
9R,10R-trans-epoxy-13R-hydroxy-11E-octadecenoic acid + H2O
(9R,10S,13R)-trihydroxy-11E-octadecenoic acid
-
-
-
?
benzopyrene 4,5-oxide + H2O
(-)benzopyrene 4,5-dihydrodiol
-
-
-
-
?
cis-1,3-diphenylpropene oxide + H2O
?
-
3.0% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
cis-14,15-epoxyeicosatrienoic acid + H2O
cis-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
cis-9,10-epoxy-12-octadecenoate methyl ester + H2O
9,10-dihydroxystearic acid methyl ester
-
6.5% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
cis-9,10-epoxystearic acid + H2O
9,10-dihydroxystearic acid
-
6.7% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
cis-stilbene oxide + H2O
1,2-diphenylethane-1,2-diol
-
0.4% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
cyano(2-methoxy-naphthalen-6-yl)methyl trans-2-(3-propyloxiran-2-yl) acetate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
cyano(6-methoxy-2-naphthyl)methyl (3,3-dimethyloxiran-2-yl)methyl carbonate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
cyano(6-methoxy-2-naphthyl)methyl (3-ethyloxiran-2-yl)methyl carbonate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
cyano(6-methoxy-2-naphthyl)methyl (3-phenyloxiran-2-yl)acetate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
cyano(6-methoxy-2-naphthyl)methyl (3-phenyloxiran-2-yl)methyl carbonate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
cyano(6-methoxy-2-naphthyl)methyl (3-propyloxiran-2-yl)methyl carbonate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
cyano(6-methoxy-2-naphthyl)methyl [3-(4-nitrophenyl)oxiran-2-yl]methyl carbonate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
cyano(6-methoxynaphthalen-2-yl)methyl (3-phenyloxiran-2-yl)acetate + H2O
[1,2-dihydroxy-2-(3-phenyloxiran-2-yl)ethoxy](6-methoxynaphthalen-2-yl)acetonitrile
-
-
-
-
?
dihydronaphthalene oxide + H2O
(1S,2S)-1,2,3,4-tetrahydronaphthalene-1,2-diol
-
-
highly enantioselective in ionic liquid [bmim][PF6]in presence of 10% water
-
?
juvenile hormone III + H2O
?
-
6.3% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
leukotriene A4 + H2O
5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid
-
-
i.e. compound D, product identification by GC-MS
-
?
racemic 4-nitrophenyl-trans-2,3-epoxy-3-phenylpropyl carbonate + H2O
?
-
-
-
-
?
trans-stilbene oxide + H2O
1,2-diphenylethane-1,2-diol
-
2.8% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
trans-stilbene oxide + H2O
?
-
-
-
-
?
[3-(4-chlorophenyl)oxiran-2-yl]methyl cyano(6-methoxy-2-naphthyl)methyl carbonate + H2O
6-methoxy-2-naphthaldehyde + CN- + ?
-
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
14,15-epoxyeicosatrienoic acid, i.e. 14,15-EET, is cytoprotective in vivo, which is in part mediated by STAT3, overview
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
i.e. 14,15-EET, EETs have antiinflammatory effects and are required for normal endothelial function
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
i.e. EETs, showing endothelium-derived hyperpolarizing factor effects dominating in microvessels independent of nitric oxide and prostacyclin. sEH reduces the beneficial effects of EETs
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
-
?
epoxyeicosatrienoic acid + H2O
dihydroxyeicosatrienoic acid
-
-
-
?
additional information
?
-
the enzyme is involved in synthesis of tetrahydrofuran diol and trihydroxy furanyl lipids, enzyme regulation, overview
-
-
?
additional information
?
-
substrate specificity, the enzyme prefers trans- over cis-epoxides of sterically hindered substrates like stilbene oxides, the C-terminal domain catalyzes epoxy fatty acid hydrolysis, the N-terminal catalytic domain has also phosphatase activity with specificity for fatty acid diol phosphates, except for the isozyme EPXH2B, overview
-
-
?
additional information
?
-
activity of the sEH can be regulated by the tyrosine nitration of the protein
-
-
?
additional information
?
-
-
activity of the sEH can be regulated by the tyrosine nitration of the protein
-
-
?
additional information
?
-
EETs are important regulators of cardiovascular function, of cerebral blood flow, and exhibit a wide array of potentially beneficial actions in stroke, including vasodilation, neuroprotection, promotion of angiogenesis and suppression of platelet aggregation, oxidative stress and postischemic inflammation, detailed overview
-
-
?
additional information
?
-
epoxyeicosatrienoic acids are substrates of sEH, enzyme regulation, overview
-
-
?
additional information
?
-
sEH catalyzes the conversion of epoxyeicosatrienoic acids, EETs, to form the corresponding dihydroxyeicosatrienoic acids, DHETs
-
-
?
additional information
?
-
-
sEH catalyzes the conversion of epoxyeicosatrienoic acids, EETs, to form the corresponding dihydroxyeicosatrienoic acids, DHETs
-
-
?
additional information
?
-
sEH rapidly hydrolyzes eicosatrienoic acids to their corresponding dihydroxyeicosatrienoic acid, DHET, metabolites, which, in general, are much less biologically active than eicosatrienoic acids. Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation, overview. functional impact of CYP epoxygenase-derived eicosatrienoic acids biosynthesis and sEH-mediated xyeicosatrienoic acids hydrolysis on key inflammatory process in the cardiovascular system
-
-
?
additional information
?
-
soluble epoxide hydrolase is an enzyme that catalyzes the hydrolysis of epoxyeicosatrienoic acids, EETs, which are lipid mediators derived from arachidonic acid through the cytochrome P450 epoxygenase pathway. EETs can activate multiple antiapoptotic targets through PI3K/Akt survival signaling and protect cardiomyocytes from hypoxia/anoxia
-
-
?
additional information
?
-
each monomer is comprised of two distinct structural domains, linked by a proline-rich segment, the 35 kDa C-terminal domain displays epoxide hydrolase activity, while the N-terminal domain exhibits phosphatase activity
-
-
?
additional information
?
-
sEH is bifunctional enzyme with C-terminal hydrolase and N-terminal phosphatase activities
-
-
?
additional information
?
-
-
sEH is bifunctional enzyme with C-terminal hydrolase and N-terminal phosphatase activities
-
-
?
additional information
?
-
the C-terminal domain of the soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids, EETs, to their less active diols, while the N-terminal domain demonstrates lipid phosphatase activity
-
-
?
additional information
?
-
the enzyme has a broad substrate range and shows high regio- and enantioselectivity for nucleophilic ring opening by Asp333
-
-
?
additional information
?
-
the sEH is a dual function enzyme that generates dihydroxy-fatty acids via its C-terminal hydrolase domain, while the N-terminal phosphatase domain has been proposed to have lipid phosphatase activity, bifunctional epoxide hydrolase 2 includes cytosolic epoxide hydrolase 2, sEH, EC 3.3.2.10, and lipid-phosphate phosphatase, EC 3.1.3.76
-
-
?
additional information
?
-
-
involvement of the Asp333-His523 pair in the catalytic mechanism
-
-
?
additional information
?
-
-
induced by parental exposure to N-ethyl-N-nitrosourea
-
-
?
additional information
?
-
-
oxygenated lipids may be endogenous substrates for the cytosolic epoxide hydrolase
-
-
?
additional information
?
-
-
enzyme inhibition decreases plasma levels of proinflammatory cytokines and nitric oxide metabolites while promoting the formation of lipoxins, thus supporting inflammatory resolution
-
-
?
additional information
?
-
-
the enzyme is involved in regulation of blood pressure and inflammation
-
-
?
additional information
?
-
-
reaction mechanism with flurogenic substrates
-
-
?
additional information
?
-
-
sEH prefers gem-di-, trans-di-, cis-di-, tri-, and tetra-substituted epoxides
-
-
?
additional information
?
-
-
substrate specificity, the microsomal enzyme rapidly hydrolyzes epoxides on cyclic systems as well as mono, 1,1-di and cis-1,2-disubstituted epoxides
-
-
?
additional information
?
-
the enzyme converts epoxyalcohols into linoleate triols
-
-
?
additional information
?
-
-
the enzyme converts epoxyalcohols into linoleate triols
-
-
?
additional information
?
-
human soluble EH (sEH or EPHX2) and human or murine epoxide hydrolase-3 (EH3 or EPHX3) hydrolyze cis or trans allylic epoxides to single diastereomers, identical to the major isomers detected in epidermis. Microsomal EH (mEH or EPHX1, EC 3.3.2.9) is inactive with these substrates. 12,13-trans-Epoxy-octadeca-9E-enoic acid is completely hydrolyzed by human sEH, human EH3, and N-truncated murine EH3 and mostly hydrolyzed using the N-truncated+7aa-insert murine EH3. 12,13-cis-Epoxy-octadeca-9E-enoic acid is hardly hydrolyzed by human EH3, N-truncated murine EH3, and the N-truncated+7aa-insert murine EH3, and 30% hydrolysis is observed using human sEH. At low substrate concentrations, EPHX2 hydrolyzes 14,15-epoxyeicosatrienoic acid (EET) at twice the rate of the epidermal epoxyalcohol, 9R,10R-trans-epoxy-11E-13R-hydroxy-octadecenoic acid, whereas human or murine EPHX3 hydrolyze the allylic epoxyalcohol at 31fold and 39fold higher rates, respectively
-
-
?
additional information
?
-
-
human soluble EH (sEH or EPHX2) and human or murine epoxide hydrolase-3 (EH3 or EPHX3) hydrolyze cis or trans allylic epoxides to single diastereomers, identical to the major isomers detected in epidermis. Microsomal EH (mEH or EPHX1, EC 3.3.2.9) is inactive with these substrates. 12,13-trans-Epoxy-octadeca-9E-enoic acid is completely hydrolyzed by human sEH, human EH3, and N-truncated murine EH3 and mostly hydrolyzed using the N-truncated+7aa-insert murine EH3. 12,13-cis-Epoxy-octadeca-9E-enoic acid is hardly hydrolyzed by human EH3, N-truncated murine EH3, and the N-truncated+7aa-insert murine EH3, and 30% hydrolysis is observed using human sEH. At low substrate concentrations, EPHX2 hydrolyzes 14,15-epoxyeicosatrienoic acid (EET) at twice the rate of the epidermal epoxyalcohol, 9R,10R-trans-epoxy-11E-13R-hydroxy-octadecenoic acid, whereas human or murine EPHX3 hydrolyze the allylic epoxyalcohol at 31fold and 39fold higher rates, respectively
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
11,12-epoxyeicosatrienoic acid + H2O
11,12-dihydroxyeicosatrienoic acid
-
-
-
?
14,15-epoxyeicosatrienoic acid + H2O
14,15-dihydroxyeicosatrienoic acid
-
-
-
?
5,6-epoxyeicosatrienoic acid + H2O
5,6-dihydroxyeicosatrienoic acid
-
-
-
?
8,9-epoxyeicosatrienoic acid + H2O
8,9-dihydroxyeicosatrienoic acid
-
-
-
?
cis-14,15-epoxyeicosatrienoic acid + H2O
cis-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(10R)-hydroxy-(11S,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoic acid + H2O
(10R,11R,12S)-trihydroxy-(5Z,8Z,14Z)-eicosatrienoic acid
-
i.e. hepoxilin B3
-
-
?
(8R)-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoic acid + H2O
(8R,11R,12S)-trihydroxy-(5Z,9E,14Z)-eicosatrienoic acid
-
i.e. hepoxilin A3, hydrolysis in liver is mainly catalyzed by soluble epoxide hydrolase
-
-
?
9R,10R-trans-epoxy-13R-hydroxy-11E-octadecenoic acid + H2O
(9R,10S,13R)-trihydroxy-11E-octadecenoic acid
-
-
-
?
cis-14,15-epoxyeicosatrienoic acid + H2O
cis-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,11Z,14Z)-8,9-epoxyeicosatrienoic acid + H2O
(5Z,11Z,14Z)-8,9-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
14,15-epoxyeicosatrienoic acid, i.e. 14,15-EET, is cytoprotective in vivo, which is in part mediated by STAT3, overview
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
i.e. 14,15-EET, EETs have antiinflammatory effects and are required for normal endothelial function
-
-
?
(5Z,8Z,11Z)-14,15-epoxyeicosatrienoic acid + H2O
(5Z,8Z,11Z)-14,15-dihydroxyeicosatrienoic acid
i.e. EETs, showing endothelium-derived hyperpolarizing factor effects dominating in microvessels independent of nitric oxide and prostacyclin. sEH reduces the beneficial effects of EETs
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
?
(5Z,8Z,14Z)-11,12-epoxyeicosatrienoic acid + H2O
(5Z,8Z,14Z)-11,12-dihydroxyeicosatrienoic acid
-
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
?
(8Z,11Z,14Z)-5,6-epoxyeicosatrienoic acid + H2O
(8Z,11Z,14Z)-5,6-dihydroxyeicosatrienoic acid
-
-
-
-
?
epoxyeicosatrienoic acid + H2O
dihydroxyeicosatrienoic acid
-
-
-
?
additional information
?
-
the enzyme is involved in synthesis of tetrahydrofuran diol and trihydroxy furanyl lipids, enzyme regulation, overview
-
-
?
additional information
?
-
activity of the sEH can be regulated by the tyrosine nitration of the protein
-
-
?
additional information
?
-
-
activity of the sEH can be regulated by the tyrosine nitration of the protein
-
-
?
additional information
?
-
EETs are important regulators of cardiovascular function, of cerebral blood flow, and exhibit a wide array of potentially beneficial actions in stroke, including vasodilation, neuroprotection, promotion of angiogenesis and suppression of platelet aggregation, oxidative stress and postischemic inflammation, detailed overview
-
-
?
additional information
?
-
epoxyeicosatrienoic acids are substrates of sEH, enzyme regulation, overview
-
-
?
additional information
?
-
sEH catalyzes the conversion of epoxyeicosatrienoic acids, EETs, to form the corresponding dihydroxyeicosatrienoic acids, DHETs
-
-
?
additional information
?
-
-
sEH catalyzes the conversion of epoxyeicosatrienoic acids, EETs, to form the corresponding dihydroxyeicosatrienoic acids, DHETs
-
-
?
additional information
?
-
sEH rapidly hydrolyzes eicosatrienoic acids to their corresponding dihydroxyeicosatrienoic acid, DHET, metabolites, which, in general, are much less biologically active than eicosatrienoic acids. Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation, overview. functional impact of CYP epoxygenase-derived eicosatrienoic acids biosynthesis and sEH-mediated xyeicosatrienoic acids hydrolysis on key inflammatory process in the cardiovascular system
-
-
?
additional information
?
-
soluble epoxide hydrolase is an enzyme that catalyzes the hydrolysis of epoxyeicosatrienoic acids, EETs, which are lipid mediators derived from arachidonic acid through the cytochrome P450 epoxygenase pathway. EETs can activate multiple antiapoptotic targets through PI3K/Akt survival signaling and protect cardiomyocytes from hypoxia/anoxia
-
-
?
additional information
?
-
-
induced by parental exposure to N-ethyl-N-nitrosourea
-
-
?
additional information
?
-
-
oxygenated lipids may be endogenous substrates for the cytosolic epoxide hydrolase
-
-
?
additional information
?
-
-
enzyme inhibition decreases plasma levels of proinflammatory cytokines and nitric oxide metabolites while promoting the formation of lipoxins, thus supporting inflammatory resolution
-
-
?
additional information
?
-
-
the enzyme is involved in regulation of blood pressure and inflammation
-
-
?
additional information
?
-
the enzyme converts epoxyalcohols into linoleate triols
-
-
?
additional information
?
-
-
the enzyme converts epoxyalcohols into linoleate triols
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-(1-acetypiperidin-4-yl)-3-adamantanylurea
APAU, a tight binding inhibitor of enzyme sEH
1-(1-methanesulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea
i.e. TUPS
1-(1-nicotinoylpiperidin-4-yl)-3-(4-(trifluoromethoxy) phenyl) urea
i.e. AR9276, reduces atherosclerotic lesions in the aorta and carotid artery and attenuates abdominal aortic aneurysm formation in apolipoprotein E-deficient mice
1-(1-nicotinoylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)-urea
i.e. AR9276
1-(3-[[3-(morpholin-4-yl)propyl]sulfonyl]phenyl)-3-[4-(trifluoromethyl)phenyl]urea
-
1-(4-chlorophenyl)-3-[4-[4-(morpholin-4-yl)benzoyl]cyclohex-2-yn-1-yl]urea
-
1-(4-trifluoro-methoxy-phenyl)-3-(1-propionylpiperidin-4-yl)urea
TPPU, a tight binding inhibitor of enzyme sEH
1-(4-[[4-(2-methoxyethyl)piperazin-1-yl]carbonyl]phenyl)-3-[4-(trifluoromethyl)phenyl]urea
-
1-adamantan-1-yl-3-{5-[2-(2-ethoxy-ethoxy)-ethoxy]-pentyl}-urea
i.e. AEPU, shows beneficial effects in cardiac hypertrophy, evaluation in a clinically relevant murine model of myocardial infarction, overview
1-[1-(methylsulfonyl)piperidin-4-yl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[4-[2-(2-ethoxyethoxy)ethoxy]cyclohexyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[4-[2-(2-ethoxyethoxy)ethoxy]phenyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[4-[2-(morpholin-4-yl)ethoxy]cyclohexyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[5-[3-(morpholin-4-yl)propoxy]pentyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[cis-4-(4-fluorophenoxy)cyclohexyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[cis-4-(4-methoxyphenoxy)cyclohexyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[cis-4-(cyclohexylmethoxy)cyclohexyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[cis-4-[(2-methylbenzyl)oxy]cyclohexyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
1-[cis-4-[(4-bromobenzyl)oxy]cyclohexyl]-3-tricyclo[3.3.1.13,7]dec-1-ylurea
-
12-(3-adamantan-1-yl-ureido)dodecanoic acid butyl ester
AUDA-BE, displays improved bioavailability compared to AUDA, can be administered ip to improve stroke outcome in a mouse model of ischemia/reperfusion injury
12-(3-adamantyl-ureido)-dodecanoic acid
AUDA, a tight binding inhibitor of enzyme sEH
2,4-dichloro-N-[4-[3-methyl-5-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]benzamide
-
2-(benzylamino)-N-[4-[3-(pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]pyridine-3-carboxamide
-
2-[2-(adamantan-1-yl)ethyl]-N-(3,5-dimethyladamantan-1-yl)hydrazine-1-carboxamide
-
2-[2-(adamantan-1-yl)ethyl]-N-[(adamantan-1-yl)methyl]hydrazine-1-carboxamide
-
2-[3-(adamantan-1-yl)propyl]-N-(3,5-dimethyladamantan-1-yl)hydrazine-1-carboxamide
-
3-([[(adamantan-1-yl)methyl]carbamoyl]amino)adamantan-1-yl trifluoroacetate
-
3-morpholinosydnonimine
i.e. SIN-1, a peroxonitrite generator, causes nitration on several tyrosine residues including Tyr383 and Tyr466. 1-adamantyl-3-cyclohexylurea in vitro decreases sensitivity to SIN-1
4'-(methylsulfonyl)-N-[4-[3-(pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]biphenyl-3-carboxamide
-
4-([cis-4-[(tricyclo[3.3.1.13,7]dec-1-ylcarbamoyl)amino]cyclohexyl]oxy)benzoic acid
-
4-[[(1r,4r)-4-([[(adamantan-1-yl)methyl]carbamoyl]amino)cyclohexyl]oxy]benzoic acid
-
4-[[(1r,4r)-4-[[(3,5,7-trimethyladamantan-1-yl)carbamoyl]amino]cyclohexyl]oxy]benzoic acid
-
4-[[(1r,4r)-4-[[(3,5-dimethyladamantan-1-yl)carbamoyl]amino]cyclohexyl]oxy]benzoic acid
-
4-[[(1r,4r)-4-[[(3-chloroadamantan-1-yl)carbamoyl]amino]cyclohexyl]oxy]benzoic acid
-
4-[[(1r,4r)-4-[[(3-ethyladamantan-1-yl)carbamoyl]amino]cyclohexyl]oxy]benzoic acid
-
4-[[(1r,4r)-4-[[(3-methyladamantan-1-yl)carbamoyl]amino]cyclohexyl]oxy]benzoic acid
-
4-[[(2R,5R)-5-[[(2-oxoadamantan-1-yl)carbamoyl]amino]piperidin-2-yl]oxy]benzoic acid
-
4-[[([4-[(4-[(2-phenylethyl)amino]-6-[[(2R)-2-phenylpropyl]amino]-1,3,5-triazin-2-yl)amino]cyclohexyl]carbonyl)amino]methyl]benzoic acid
-
4-[[4-(azepan-1-yl)-6-(methylamino)-1,3,5-triazin-2-yl]amino]-N-[2-(trifluoromethoxy)benzyl]cyclohexanecarboxamide
-
4-[[4-([[4-(trifluoromethyl)phenyl]carbamoyl]amino)cyclohexyl]sulfonyl]benzoic acid
-
6-cyano-N-[3-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]propyl]-1,6-dihydropyridine-3-carboxamide
-
7-butyl-N-(2,3-dimethoxybenzyl)-6-(3,4,5-trimethoxyphenyl)-7H-cyclopenta[b]pyridine-3-carboxamide
-
AR9276
a potent, orally bioavailable, ans selective sEH inhibitor, pharmacokinetics and clearance, overview. Lowers the cholesterol levels a nd attenuates abdominal aortic aneurysm formation. It also reduces lesions in thew aortic arch and nonliganted right carotid artery, but has no effect on ligation-induced vascular remodeling in the carotid artery, overview
N,N'-butane-1,4-diylbis[N'-[1-(adamantan-1-yl)-2-methylpropan-2-yl]urea]
-
N,N'-[1,4-phenylenebis(methylene)]bis[N'-(3,5-dimethyladamantan-1-yl)urea]
-
N-(2,4-dichlorobenzyl)-1-[(2,4,6-trimethylphenyl)sulfonyl]piperidine-4-carboxamide
-
N-(2-oxoadamantan-1-yl)-N'-1,3,5-triazatricyclo[3.3.1.13,7]decan-7-ylurea
-
N-(3,5,7-trimethyladamantan-1-yl)-4-([[(3,5,7-trimethyladamantan-1-yl)carbamoyl]amino]methyl)piperidine-1-carboxamide
-
N-(3,5-dimethyladamantan-1-yl)-N'-1,3,5-triazatricyclo[3.3.1.13,7]decan-7-ylurea
-
N-(3,5-dimethyladamantan-1-yl)-N'-[4-([[(3,5-dimethyladamantan-1-yl)carbamoyl]amino]methyl)phenyl]urea
-
N-(3-ethyladamantan-1-yl)-N'-1,3,5-triazatricyclo[3.3.1.13,7]decan-7-ylurea
-
-
N-(4-chlorophenyl)-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxamide
-
N-adamantan-1-yl-N'-(5-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]pentyl)urea
-
N-adamantan-1-yl-N'-[5-[2-(2-ethoxyethoxy)ethoxy]pentyl]urea
AEPU, a tight binding inhibitor of enzyme sEH
N-cycloheptyl-1-[(2,4,6-trimethylphenyl)sulfonyl]piperidine-4-carboxamide
-
N-[(3,5-dimethyladamantan-1-yl)methyl]-N'-(3,5,7-trimethyladamantan-1-yl)urea
-
N-[(3-chloro-4'-fluorobiphenyl-4-yl)methyl]-6-[3-(trifluoromethoxy)phenoxy]pyridine-3-carboxamide
-
N-[(3-ethyladamantan-1-yl)methyl]-N'-1,3,5-triazatricyclo[3.3.1.13,7]decan-7-ylurea
-
N-[(adamantan-1-yl)methyl]-2-[3-(adamantan-1-yl)propyl]hydrazine-1-carboxamide
-
N-[(adamantan-1-yl)methyl]-4-[([[(adamantan-1-yl)methyl]carbamoyl]amino)methyl]piperidine-1-carboxamide
-
N-[1-(1-oxopropyl)-4-piperidinyl]-N0-[4-(trifluoromethoxy)phenyl]-urea
TPPU
N-[2-[4-(benzyloxy)phenyl]ethyl]-2-hydroxy-4-(tricyclo[3.3.1.13,7]dec-1-yl)butanamide
-
N-[4-bromo-2-(trifluoromethoxy)benzyl]-6-(4-fluorophenyl)pyridine-3-carboxamide
-
N-[4-[(4-chlorophenyl)sulfonyl]cyclohexyl]-2-hydroxy-2-(tricyclo[3.3.1.13,7]dec-1-yl)acetamide
-
N-[4-[3-(pyridin-3-yl)-5-(trifluoromethyl)-1H-pyrazol-1-yl]benzyl]pyridine-3-carboxamide
-
N-[5-[2-(2-ethoxyethoxy)ethoxy]pentyl]-N'-(4-hydroxyadamantan-1-yl)urea
-
N-[[4-([[4-(trifluoromethyl)phenyl]carbamoyl]amino)phenyl]sulfonyl]-b-alanine
-
N1-(2,4-dichlorobenzyl)-N4-(2-methoxyethyl)piperidine-1,4-dicarboxamide
-
peroxynitrite
causes nitration on several tyrosine residues including Tyr383 and Tyr466
trans-4-(4-(3-adamantan-1-yl-ureido)-cyclohexyloxy)-benzoic acid
i.e. t-AUCB
trans-4[4-(3-adamantanyl-1-yl-ureido)cyclohexyloxy]-benzoic acid
i.e.tAUCB
(1S,2S)-1,2-epoxy-1-phenyl-1-propane
-
weak inhibition, IC50 is 2.4 mM, preincubation of enzyme with inhibitor does not influence the inhibitory effect
(2R,3R)-2,3-epoxy-3-(4-nitrophenyl)glycidol
-
IC50 is 1.2 mM, the S-enantiomer is a 750fold better inhibitor compared to the R-isomer
(2R,3R)-3-(4-bromophenyl)glycidol
-
preincubation of enzyme with inhibitor increases the inhibitory effect
(2S,3S)-1-acetoxy-2,3-epoxy-3-(4-nitrophenyl)propane
-
IC50 is 0.012 mM, preincubation of enzyme with inhibitor decreases the inhibitory effect
(2S,3S)-1-ethoxy-2,3-epoxy-3-(4-nitrophenyl)propane
-
IC50 is 0.012 mM, preincubation of enzyme with inhibitor decreases the inhibitory effect
(2S,3S)-2,3-epoxy-3-(4-nitrophenyl)glycidol
-
IC50 is 0.0016 mM, the S-enantiomer is a 750fold better inhibitor compared to the R-isomer
(2S,3S)-3-(4-nitrophenyl)glycidol
-
preincubation of enzyme with inhibitor increases the inhibitory effect
1,3-disubstituted amides
-
potent and stable inhibition, Ki in the nanomolar range, mechanism
1,3-disubstituted carbamate derivatives
-
potent and stable inhibition, Ki in the nanomolar range, mechanism
1,3-disubstituted urea derivatives
-
potent and stable inhibition, Ki in the nanomolar range, mechanism
1-(1-methanesulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea
-
0.001 mM markedly inhibits the basal and angiotensin II-induced sEH activity
1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea
-
potent inhibitor of sEH
1-adamantan-1-yl-3-(5-[2-(2-ethoxyethoxy)ethoxy]pentyl)urea
-
i.e. 1-adamantan-1-yl-3-(5-[2-(2-ethoxyethoxy)ethoxy]pentyl)urea
1-adamantan-3-(5-(2-(2-ethylethoxy)ethoxy)pentyl)urea
-
highly potent and selective sEH inhibitor
12-(3-adamantan-1-yl-ureido)dodecanoic acid butyl ester
-
highly potent sEH inhibitor
2-methylglycidyl 4-nitrobenzoate
-
IC50 for the S-enantiomer is 0.717 mM, the R-enantiomer shows 25% inhibition at 0.2 mM
3,3-dimethylglycidyl 4-nitrobenzoate
-
IC50 for the S-enantiomer is 0.012 mM, 23% inhibition at 5 mM of the R-enantiomer
4-(5-phenyl-3-[3-[3-(4-trifluoromethyl-phenyl)-ureido]-propyl]-pyrazol-1-yl)-benzenesulfonamide
-
dual inhibitor of cyclooxygenase-2 and soluble epoxide hydrolase. Inhibitor shows the best pharmacokinetic profiles in both mice and rats. Following subcutaneous administration at 10 mg/kg, compound exhibits antiallodynic activity that is more effective than the same dose of either COX-2 inhibitor celecoxib or sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid alone, as well as coadministration of both inhibitors
carbodiimide/glycine methyl ester
-
65% inhibition at 1 mM at pH 5.2, 17% at pH 7.4
glycidyl 4-nitrobenzoate
-
IC50 for the S-enantiomer is 0.14 mM, and for the R-enantiomer 0.51 mM
trans-1-phenylpropylene oxide
-
IC50 for the S-enantiomer is 3.47 mM, and for the R-enantiomer 2.98 mM
trans-2-methyl-3-phenylglycidol
-
IC50 for the S-enantiomer is 1.52 mM, and for the R-enantiomer 2.0 mM
trans-3-(4-bromophenyl)glycidol
-
IC50 for the S-enantiomer is 0.12 mM, and for the R-enantiomer 0.77 mM
trans-3-(4-nitrophenyl)glycidol
-
IC50 for the S-enantiomer is 0.013 mM, and for the R-enantiomer 4.24 mM
trans-3-(4-nitrophenyl)glycidyl acetate
-
IC50 for the S-enantiomer is 0.232 mM, and for the R-enantiomer 0.39 mM
trans-3-(4-nitrophenyl)glycidyl benzoate
-
IC50 for the S-enantiomer is 0.229 mM, and for the R-enantiomer 0.10 mM
trans-3-methylglycidyl 4-nitrobenzoate
-
the S-enantiomer shows 20% inhibition at 0.8 mM, the R-enantiomer 16.5% inhibition at 0.8 mM
trans-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid
-
potent sEH inhibitor
[3-(4-phenoxycyclohexa-1,5-dien-1-yl)oxiran-2-yl](phenyl)methanone
-
IC50 is 0.00014 mM
[4-(bromomethyl)phenyl][3-(2-naphthyl)oxiran-2-yl]methanone
-
IC50 is 0.00011 mM
12-(3-adamantan-1-yl-ureido)-dodecanoic acid
i.e. AUDA, binding structure, overview
trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid
i.e. t-AUCB, causes enzyme inhibition that is protective against ischemia-reperfusion injury, reversible by 14,15-epoxyeicosatrienoic acid, mechanisms, overview
trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid
i.e. tAUCB, shows beneficial effects in cardiac hypertrophy, evaluation in a clinically relevant murine model of myocardial infarction, overview
trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid
i.e. t-AUCB
trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid
t-AUCB, a tight binding inhibitor of enzyme sEH
trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]-benzoic acid
i.e. t-AUCB
12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester
-
i.e. AUDA-BE, physiologic consequences of enzyme inhibition in vivo
12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester
-
selective sEH inhibitor
12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester
-
selective soluble epoxide hydrolase inhibitor
12-(3-adamantan-1-yl-ureido)dodecanoic acid
-
potent transition state inhibitor of sEH
12-(3-adamantan-1-yl-ureido)dodecanoic acid
-
selective soluble epoxide hydrolase inhibitor
12-(3-adamantan-1-ylureido)-dodecanoic acid
-
very potent sEH inhibitor, sEH inhibitor treatment was not associated with an attenuation of lipopolysaccharide-induced inflammatory gene expression in the liver, and 12-(3-adamantan-1-ylureido)-dodecanoic acid does not protect from lipopolysaccharide-induced neutrophil infiltration
Clofibrate
-
slight inhibition of enzyme from untreated mice, slight activation of the enzyme from clofibrate-treated mice
tetrahydrofuran
-
73% loss of activity with 1% tetrahydrofuran, 98% loss of activity with 5% tetrahydrofuran
additional information
administration of an sEH inhibitor significantly attenuates LPS-mediated induction of hepatic COX-2 expression and circulating PGE2 levels in mice
-
additional information
design and synthesis of small molecule enzyme inhibitors
-
additional information
inhibition of soluble epoxide hydrolase attenuated atherosclerosis, abdominal aortic aneurysm formation, and dyslipidemia. It downregulates the expression of proinflammatory mediators in the aortic tissue and in the blood
-
additional information
-
inhibition of soluble epoxide hydrolase attenuated atherosclerosis, abdominal aortic aneurysm formation, and dyslipidemia. It downregulates the expression of proinflammatory mediators in the aortic tissue and in the blood
-
additional information
intervention with fish oil, but not with docosahexaenoic acid, results in significantly lower levels of hepatic sEH levels with time compared with high-oleic acid sunflower-seed oil, but the treatment does not influence atherosclerosis
-
additional information
the EET antagonist, 14,15-EEZE at 10 mM attenuates the increase in pulmonary artery pressure in the absence of the sEH inhibitor and completely prevents the increased constriction induced by 1-adamantyl-3-cyclohexylurea. Prolonged sEH inhibition results in significantly elevated serum levels of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids/dihydroxyeicosatrienoic acids but fails to affect the ratio of the right/left ventricle and septum
-
additional information
treatment with sEH inhibitors reduces blood pressure in several animal models of hypertension
-
additional information
differential effects of pharmarcological inhibition and genetic deletion of sEH on status epilepticus-induced cytokine expressions and ictogenesis, overview
-
additional information
-
differential effects of pharmarcological inhibition and genetic deletion of sEH on status epilepticus-induced cytokine expressions and ictogenesis, overview
-
additional information
in vitro and in vivo metabolism of N-adamantyl substituted urea-based soluble epoxide hydrolase inhibitors, identification of ligands structures by mass spectrometry and NMR spectroscopy, overview
-
additional information
inhibitory potency and metabolic stability of adamantyl ureas and diureas bearing substituents in bridgehead positions of adamantane and/or spacers between urea groups and adamantane group. Comparison of the effects of the inhibitors on human, rat, and murine enzymes, overview
-
additional information
-
inhibitory potency and metabolic stability of adamantyl ureas and diureas bearing substituents in bridgehead positions of adamantane and/or spacers between urea groups and adamantane group. Comparison of the effects of the inhibitors on human, rat, and murine enzymes, overview
-
additional information
-
cyclohexandione is a poor inhibitor, no inhibition by amino-, guanido-, or activated serine-selective reagents
-
additional information
-
IC50 values with different substrates and structure-activity relationships of enzyme inhibitors, development of an in vitro inhibition assay using fluorogenic substrates
-
additional information
-
inhibitor synthesis, overview, inhibition mechanisms, overview
-
additional information
-
irreversible inhibition mechanism of chalcone oxide derivatives, quantitative structure-activity relationship, QSAR, overview
-
additional information
-
no inhibition by Fe2+ and Fe3+ at 1 mM, metal chelators like 1,10-phenanthroline, 1,7-phenanthroline, EDTA, EGTA, and dipicolinic acid preserve enzyme activity in presence of metal ions
-
additional information
-
quantitative structure-activity relationship, QSAR, and classification in a five-discriptor model of enzyme inhibition by 348 urea-like compounds, IC50 ranging from 60 nM to 0.5 mM, overview
-
additional information
-
sterical differences play a role in inhibitory potency
-
additional information
-
lipopolysaccharide has an effect on sEH expression and function, as evident from a significant down-regulation of Ephx2 mRNA
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Clofibrate
-
slight inhibition of enzyme from untreated mice, slight activation of the enzyme from clofibrate-treated mice
additional information
-
the enzyme is induced by several substances, e.g. 2-acetylfluorene, alpha-1-acetylmethadol, butylated hydroxyanisole, butylated hydroxytoluene, chalcone, gamma-chlordane, 1,2-dibromo-3-chloropropane, ethoxyquin, isosafrole, 3-methylcholanthrene, alpha-naphthoflavone, phenobarbital, polychlorinated and/or polybrominated biphenyls, pregnenolone-16alpha-carbonitrile, and trans-stilbene oxide
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.015
4-nitrophenyl (2R,3R)-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate
-
pH 7.4, 25°C
0.008
4-nitrophenyl (2S,3S)-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate
-
pH 7.4, 25°C
additional information
additional information
-
kinetics, the hydrolysis of the intermediate is the rate-limiting step
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4.8
4-nitrophenyl (2R,3R)-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate
-
pH 7.4, 25°C
7.7
4-nitrophenyl (2S,3S)-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate
-
pH 7.4, 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000345
4-[[(1r,4r)-4-[[(3,5,7-trimethyladamantan-1-yl)carbamoyl]amino]cyclohexyl]oxy]benzoic acid
Mus musculus
pH 7.4, 37°C
0.000436
N-(3,5,7-trimethyladamantan-1-yl)-4-([[(3,5,7-trimethyladamantan-1-yl)carbamoyl]amino]methyl)piperidine-1-carboxamide
Mus musculus
pH 7.4, 37°C
0.0000052
N-(3,5-dimethyladamantan-1-yl)-N'-(1-propanoylpiperidin-4-yl)urea
Mus musculus
pH 7.4, 37°C
0.011376
N-(3,5-dimethyladamantan-1-yl)-N'-(3,5,7-trimethyladamantan-1-yl)urea
Mus musculus
pH 7.4, 37°C
0.0001069
N-adamantan-1-yl-N'-(3,5,7-trimethyladamantan-1-yl)urea
Mus musculus
pH 7.4, 37°C
0.000003
N-adamantan-1-yl-N'-[5-[2-(2-ethoxyethoxy)ethoxy]pentyl]urea
Mus musculus
pH 7.4, 37°C
0.000006
N-adamantan-1-yl-N'-[5-[2-(2-hydroxyethoxy)ethoxy]pentyl]urea
Mus musculus
pH 7.4, 37°C
2.4
(1S,2S)-1,2-epoxy-1-phenyl-1-propane
Mus musculus
-
weak inhibition, IC50 is 2.4 mM, preincubation of enzyme with inhibitor does not influence the inhibitory effect
1.2
(2R,3R)-2,3-epoxy-3-(4-nitrophenyl)glycidol
Mus musculus
-
IC50 is 1.2 mM, the S-enantiomer is a 750fold better inhibitor compared to the R-isomer
0.012
(2S,3S)-1-acetoxy-2,3-epoxy-3-(4-nitrophenyl)propane
Mus musculus
-
IC50 is 0.012 mM, preincubation of enzyme with inhibitor decreases the inhibitory effect
0.012
(2S,3S)-1-ethoxy-2,3-epoxy-3-(4-nitrophenyl)propane
Mus musculus
-
IC50 is 0.012 mM, preincubation of enzyme with inhibitor decreases the inhibitory effect
0.0016
(2S,3S)-2,3-epoxy-3-(4-nitrophenyl)glycidol
Mus musculus
-
IC50 is 0.0016 mM, the S-enantiomer is a 750fold better inhibitor compared to the R-isomer
0.00028
(3-[4-(benzyloxy)phenyl]oxiran-2-yl)(phenyl)methanone
Mus musculus
-
IC50 is 0.00028 mM
0.00014
(4-bromophenyl)[3-(2-naphthyl)oxiran-2-yl]methanone
Mus musculus
-
IC50 is 0.00014 mM
0.00009
(4-methylphenyl)[3-(2-naphthyl)oxiran-2-yl]methanol
Mus musculus
-
IC50 is 0.00009 mM
0.0001
(4-methylphenyl)[3-(2-naphthyl)oxiran-2-yl]methanone
Mus musculus
-
IC50 is 0.00010 mM
0.000005
1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea
Mus musculus
-
-
0.000003
1-adamantan-1-yl-3-(5-[2-(2-ethoxyethoxy)ethoxy]pentyl)urea
Mus musculus
-
pH 7.5, 30°C
0.000003
1-adamantan-3-(5-(2-(2-ethylethoxy)ethoxy)pentyl)urea
Mus musculus
-
purified recombinant enzyme
0.000097
1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl)urea
Mus musculus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.00001
12-(3-adamantan-1-yl-ureido)dodecanoic acid
Mus musculus
-
purified recombinant enzyme
0.00001
12-(3-adamantan-1-ylureido)dodecanoic acid
Mus musculus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.000004
12-(3-adamantan-1-ylureido)dodecanoic acid butyl ester
Mus musculus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.103
2-cyclohexa-1,5-dien-1-yl-3-[methoxy(phenyl)methyl]oxirane
Mus musculus
-
IC50 is 0.103 mM
0.717
2-methylglycidyl 4-nitrobenzoate
Mus musculus
-
IC50 for the S-enantiomer is 0.717 mM, the R-enantiomer shows 25% inhibition at 0.2 mM
0.012
3,3-dimethylglycidyl 4-nitrobenzoate
Mus musculus
-
IC50 for the S-enantiomer is 0.012 mM, 23% inhibition at 5 mM of the R-enantiomer
0.00008
4-([3-(2-naphthyl)oxiran-2-yl]carbonyl)benzoic acid
Mus musculus
-
IC50 is 0.00008 mM
0.103
4-([3-(4-fluorophenyl)oxiran-2-yl]carbonyl)benzoic acid
Mus musculus
-
IC50 is 0.103 mM
0.000004
cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid
Mus musculus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.000009
N-(1-acetylpiperidin-4-yl)-N'-(adamant-1-yl)urea
Mus musculus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.032
racemic 2,3-epoxy-3-(4-fluorophenyl)-1-phenyl-1-propanol
Mus musculus
-
IC50 is 0.032 mM
0.0017
racemic 2,3-epoxy-3-(4-nitrophenyl)-1-phenyl-1-propanol
Mus musculus
-
IC50 is 0.0017 mM
0.000008
trans-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid
Mus musculus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.000008
trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid
Mus musculus
-
pH 7.5, 30°C
0.00013
[3-(2-naphthyl)oxiran-2-yl](4-nitrophenyl)methanone
Mus musculus
-
IC50 is 0.00013 mM
0.00047
[3-(4-isopropylphenyl)oxiran-2-yl](phenyl)methanone
Mus musculus
-
IC50 is 0.00047 mM
0.00014
[3-(4-phenoxycyclohexa-1,5-dien-1-yl)oxiran-2-yl](phenyl)methanone
Mus musculus
-
IC50 is 0.00014 mM
0.00011
[4-(bromomethyl)phenyl][3-(2-naphthyl)oxiran-2-yl]methanone
Mus musculus
-
IC50 is 0.00011 mM
0.00006 - 0.5
additional information
Mus musculus
-
quantitative structure-activity relationship, QSAR, and classification in a five-discriptor model of enzyme inhibition by 348 urea-like compounds, IC50 ranging from 60 nM to 0.5 mM, overview
-
0.00008
N-[5-[2-(2-ethoxyethoxy)ethoxy]pentyl]-N'-(4-hydroxyadamantan-1-yl)urea
Mus musculus
pH 7.4, 37°C
0.00029
N-[5-[2-(2-ethoxyethoxy)ethoxy]pentyl]-N'-(4-hydroxyadamantan-1-yl)urea
Mus musculus
pH 7.4, 37°C
0.232
trans-3-(4-nitrophenyl)glycidyl acetate
Mus musculus
-
IC50 for the S-enantiomer is 0.232 mM
0.39
trans-3-(4-nitrophenyl)glycidyl acetate
Mus musculus
-
IC50 for the R-enantiomer 0.39 mM
0.1
trans-3-(4-nitrophenyl)glycidyl benzoate
Mus musculus
-
IC50 for the R-enantiomer 0.10 mM
0.229
trans-3-(4-nitrophenyl)glycidyl benzoate
Mus musculus
-
IC50 for the S-enantiomer is 0.229 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.01
-
purified recombinant enzyme, substrate cyano(6-methoxy-2-naphthyl)methyl (3,3-dimethyloxiran-2-yl)methyl carbonate
0.13
-
purified recombinant enzyme, substrate cyano(6-methoxy-2-naphthyl)methyl (3-ethyloxiran-2-yl)methyl carbonate
0.21
-
purified recombinant enzyme, substrate cyano(6-methoxy-2-naphthyl)methyl (3-phenyloxiran-2-yl)acetate
0.26
-
purified recombinant enzyme, substrate cyano(6-methoxy-2-naphthyl)methyl (3-propyloxiran-2-yl)methyl carbonate
0.28
-
purified recombinant enzyme, substrate cyano(2-methoxy-naphthalen-6-yl)methyl trans-2-(3-propyloxiran-2-yl) acetate
0.78
-
purified recombinant enzyme, substrate cyano(6-methoxy-2-naphthyl)methyl (3-phenyloxiran-2-yl)methyl carbonate
0.86
1.04
-
purified recombinant enzyme, substrate [3-(4-chlorophenyl)oxiran-2-yl]methyl cyano(6-methoxy-2-naphthyl)methyl carbonate
additional information
0.86
-
purified recombinant enzyme, substrate cyano(6-methoxy-2-naphthyl)methyl [3-(4-nitrophenyl)oxiran-2-yl]methyl carbonate
additional information
sEH activities in male, female, and ovariectomized female wild-type and sEH knockout mice
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.4
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 6
maximal activity at pH 5.0, 70% of maximal activity at pH 6.0, no activity at pH 7.0-8.0, with allylic epoxyalcohols as substrates
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37 - 55
-
37°C: about 60% of maximal activity, 55°C: about 50% of maximal activity of the enzyme from clofibrate-treated animals, about 80% of maximal activity of the enzyme from untreated animals
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
661922, 663199, 695933, 707303, 707309, 707927, 708022, 708238, 708266, 709248, 731291, 752930, 753120, 755285
SwissProt
wild-type and deoxycorticosterone acetate plus high salt, i.e. DOCA-salt, hypertensive mice, gene EPHX2
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
high level of expression of sEH in atrial and ventricular myocytes
-
sEH is synthesized in adipocytes and expression levels increase upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels do not differ in the fat pads from mice receiving a regular or a high-fat diet, total adipose sEH activity is higher in the obese mice. Peroxisome proliferator-activated receptor gamma agonists increase the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo
EH3 is highly expressed in the skin, the highest expression of EH3 mRNA is in the outer epidermis where the water permeability barrier is formed
additional information
in vascular smooth muscle and endothelial cell layersm in white matter. sEH in rodent brain is neither vascular nor glial, but rather neuronal. In brain parenchymal tissue, sEH is markedly expressed in neuronal cell bodies and processes, particularly within the cerebral cortex and striatum
sEH distribution, immunohistochemical analysis, overview. sEH immunoreactivity is almost exclusively located in astrocytes throughout the brain, except in the central amygdala, where neurons are also positive for sEH
wide expression of sEH in cortical and hippocampal astrocytes and also in a few specific neuron types in the cortex, cerebellum, and medulla, immunohistochemical analysis, overview
expression of sEH is significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced status epilepticus
in the hippocampus of wild-type mice, sEH is mainly expressed in astrocytes (GFAP+), neurons (NeuN+) and scattered microglia (Iba-1+) in the regions of CA1, CA3 and dentate gyrus, immunohistochemical analysis
distribution in proximal tubules but not in the glomerulus or other regions, immunohistochemic analysis
diabetes reduces the amount of sEH protein in the liver and insulin restored the level of protein
sEH protein and expression levels during treatment with different dietary oils, overview
immunohistochemical analysis showing the expression of the sEH in lungs from wild-type mice kept under normoxic conditions or after exposure to 21 days hypoxia, overview
-
-
208896, 208902, 208904, 208905, 208906, 208910, 208914, 208928, 208929, 208931, 660713, 661024, 661511, 661717, 661890, 662085, 663434, 698863, 699754, 715837
additional information
cerebrovascular expression and activity of sEH and plasma 14,15-dihydroxyeicosatrienoic acid content are lower in wild-type female than male mice, overview
additional information
clinically relevant murine model of myocardial infarction
additional information
-
clinically relevant murine model of myocardial infarction
additional information
sEH is expressed and metabolically active in various tissues and cell types, including endothelial cells and cardiomyocytes
additional information
sEH tissue distribution, no activity in lung, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
in some cell types sEH shows a dual localisation, both cytosolic and peroxisomal
-
-
-
-
208896, 208902, 208904, 208905, 208906, 208910, 208914, 208929, 208930, 208931, 660713, 661024, 661511, 661890, 662085, 663434
-
a recombinant modified enzyme in HeLa cells, recombinant wild-type enzyme and recombinant modified enzyme in plant BY-2 cells
additional information
-
highest level found in smooth endoplasmic reticulum, lower levels observed in rough endoplasmic reticulum, Golgi apparatus, nuclear membrane and plasma membrane. The enzyme is synthesized in membrane-bound polysomes and inserted cotranslationally into the endoplasmic reticulum
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
physiological function
additional information
malfunction
acute hypoxic vasoconstriction in sEH-/- mice is insensitive to sEH inhibition but inhibited by the epoxyeicosatrienoic acid antagonist, and chronic hypoxia induces an exaggerated pulmonary vascular remodelling. In wild-type mice, chronic sEH inhibition increases serum epoxyeicosatrienoic acid levels but fails to affect acute hypoxic vasoconstriction, right ventricle weight, pulmonary artery muscularization, or voluntary running distance
malfunction
administration of an sEH inhibitor significantly attenuates LPS-mediated induction of hepatic COX-2 expression and circulating PGE2 levels in mice. Inhibition of sEH-mediated EET hydrolysis has also significantly reduced cerebral infarct volume in rodents after middle cerebral artery occlusion. sEHI treatment downregulates proinflammatory gene expression in the aorta and circulating levels in serum, and reduces inflammatory cell infiltration into the vascular wall
malfunction
association of sEH gene Ephx2 polymorphisms with increased risk of atherosclerosis and cardiovascular diseases, role of epoxyeicosatrienoic acids, EETs, and sEH in the pathogenesis of atherosclerosis, overview
malfunction
beneficial effects of several potent soluble epoxide hydrolase inhibitors in cardiac hypertrophy
malfunction
blood flow during middle cerebral artery occlusion is higher and infarct size is smaller in wild-type female compared with male mice, overview. Sex differences in cerebral blood flow and ischemic damage are abolished after ovariectomy and are absent in sEH knockout mice
malfunction
diabetes is one of the main factors responsible for end-stage renal disease caused by impaired endothelium
malfunction
in vivo, streptozotocin-induced diabetes results in the tyrosine nitration of the sEH in murine lungs and a significant decrease in its activity. Inhibition of sEH has beneficial effects on vascular inflammation and hypertension
malfunction
polymorphimsm in gene EPHX2 are associated with ischemic stroke risk. sEH inhibition and gene deletion reduce infarct size after focal cerebral ischemia in mice
malfunction
sEH knockout and its inhibition prevent hyperglycemia in diabetes, and sEH knockoit also enhances islet GSIS through the amplifying pathway and decreases islet cell apoptosis in diabetes, overview
malfunction
soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice
malfunction
treatment of apolipoprotein E-deficient mice with sEH inhibitors significantly attenuates atherosclerosis development and abdominal aortic aneurysm formation
malfunction
deletion of sEH decreases expression of HMG-CoA reductase, fatty acid synthase, and low density lipoprotein receptor. Sterol regulatory element binding proteins (SREBPs) regulate the expression of all three enzymes and SREBP activation is attenuated in the absence of sEH. The effect is attributed to the AMPK-activated protein kinase (AMPK) which is activated in the absence of sEH. Livers from wild-type versus sEH-/- littermates contain significantly higher levels of the sEH substrate 12,13-epoxyoctadecenoic acid, which elicits dAMPK activation, while the corresponding sEH product is inactive. Thus, AMPK activation and subsequent inhibition of SREBP can account for the altered expression of lipid metabolizing enzymes in sEH-/- mice
malfunction
expression of sEH is significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced status epilepticus (SE). Administration with sEH inhibitors attenuates the SE-induced up-regulation of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), the degradation of epoxyeicosatrienoic acids, as well as IkappaB phosphorylation. Following treatment with inhibitor AUDA, the frequency and duration of spontaneous motor seizures in the pilocarpine-SE mice are decreased and the seizure-induction threshold of the fully kindled mice is increased. Upregulation of hippocampal IL-1beta and IL-6 is found in both wild-type and sEH knockout mice after successful induction of SE. sEH KO mice are more susceptible to seizures than wild-type mice. Seizure related neuroinflammation and ictogenesis are attenuated by pharmacological inhibition of sEH enzymatic activity but not by sEH genetic deletion. Behavior monitoring of convulsive spontaneous recurrent seizures in the pilocarpine-induced SE model
metabolism
epoxide hydrolases comprise a family of enzymes important in detoxification and conversion of lipid signaling molecules, namely epoxyeicosatrienoic acids. Soluble epoxide hydrolase mediates the bulk of the cerebral epoxyeicosatrienoic acid metabolism, overview
metabolism
soluble epoxide hydrolase is a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids, EETs
metabolism
soluble epoxide hydrolase is the major enzyme responsible for the metabolism and inactivation of epoxyeicosatrienoic acids, EETs
physiological function
sEH is a xenobiotic-metabolizing enzyme that metabolizes epoxides to produce vicinal diols. Epoxyeicosatrienoic acids are substrates of sEH and have important roles in renal function such as ion transport and the proliferation of cells and the action of epoxyeicosatrienoic acids is important for maintaining renal and vascular homeostasis
physiological function
sEH is an enzyme involved in the metabolism of endogenous inflammatory and antiapoptotic mediators
physiological function
sEH is responsible for renal protection with DOCA-salt hypertension
physiological function
soluble epoxide hydrolase is a key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids, EETs
physiological function
soluble epoxide hydrolase is a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids, EETs, and is sexually dimorphic and suppressed by estrogen
physiological function
soluble epoxide hydrolase is the major enzyme responsible for the metabolism and inactivation of epoxyeicosatrienoic acids, EETs. In the central nervous system, EETs are thought to play a role in the regulation of local blood flow, protection from ischemic injury, inhibition of inflammation, the release of peptide hormones and modulation of fever
physiological function
mammalian soluble epoxide hydrolase (sEH) is involved in mediating the metabolism of the endogenous lipids epoxides such as epoxyeicosatrienoic acids (EETs) that are derived from arachidonic acid. The sEH converts epoxide-containing substrates into the corresponding more polar and less potent vicinal diols. EETs are vasodilation mediators through the activation of the Ca2+-activated K+-channels in endothelial cells which benefit many renal and cardiovascular diseases. EETs are reported to be involved in the cell angiogenesis and proliferation which may offer a protective role in ischemic and reperfusion injury. Furthermore, the EETs are anti-inflammatory mediators in endothelial cells by inhibiting the expression of the proatherogenic mediator vascular cell adhesion molecule-1 that is induced by tumor necrosis factor-alpha (TNF-alpha). In addition, EETs suppress the NF-kappaB-mediated expression of cytokines by activating PPARgamma
physiological function
soluble epoxide hydrolase (sEH) is a key enzyme in the metabolic conversion of epoxyeicosatrienoic acids into their less active form, dihydroxyeicosatrienoic acids (DHET). Enzyme sEH may play an important role in the generation of epilepsy. It may have clinical therapeutic implication for epilepsy in the future, particularly when treating temporal lobe epilepsy
malfunction
-
enzyme knockout mice are more susceptible to seizures than wild type mice
malfunction
-
the increased epoxyeicosatrienoic acid bioavailability, as a function of deficiency/inhibition of soluble epoxide hydrolase, potentiates vasodilator responses that counteract pressure-induced vasoconstriction to lower blood pressure
physiological function
-
hepoxilin hydrolase activity is abolished in liver preparations from sEH-/- mice, and liver homogenates of sEH-/- mice show elevated basal levels of hepoxilins but lowered levels of trioxilins compared with wild-type animals
physiological function
-
soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney
physiological function
-
the enzyme plays an important role in the generation of epilepsy
physiological function
activities of EPHX2 and EPHX3 in production of the linoleate triols detected as end products of the 12R-lipoxygenase pathway in the epidermis and functioning in formation of the mammalian water permeability barrier
additional information
cardioprotective roles of sEH inhibition in myocardial ischemia-reperfusion injury
additional information
enzyme inhibition protects against ischemic stroke, mechanism and cytoprotective, anti-inflammatory, and other effects, overview
additional information
inhibition of soluble epoxide hydrolase attenuated atherosclerosis, abdominal aortic aneurysm formation, and dyslipidemia
additional information
-
inhibition of soluble epoxide hydrolase attenuated atherosclerosis, abdominal aortic aneurysm formation, and dyslipidemia
additional information
inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model, detailed overview
additional information
-
inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model, detailed overview
additional information
treatment with sEH inhibitors reduces blood pressure in several animal models of hypertension
additional information
evaluation of different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty acid epoxides and comparison to the products to those of acid-catalyzed hydrolysis
additional information
-
evaluation of different epoxide hydrolase (EH) enzymes in the hydrolysis of skin-relevant fatty acid epoxides and comparison to the products to those of acid-catalyzed hydrolysis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HYES_MOUSE
554
0
62515
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
62000
130000
59000
60000
59000
-
1 * 59000, monomeric and dimeric enzyme forms retain catalytic activity, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
dimer
monomer
additional information
monomer
-
1 * 59000, monomeric and dimeric enzyme forms retain catalytic activity, SDS-PAGE
additional information
the 25 kDa C-terminal part, with a different hydrolase alpha/beta-fold, harbors the epoxide hydrolase activity, the enzyme's phosphatase activity of EC3.1.3.76 is located at the 35 kDa N-terminal part which has a alpha/beta-fold, structure analysis
additional information
the C-terminal domain catalyzes epoxy fatty acid hydrolysis, the N-terminal catalytic domain has also phosphatase activity with specificity for fatty acid diol phosphates
additional information
each monomer is comprised of two distinct structural domains, linked by a proline-rich segment, the 35 kDa C-terminal domain displays epoxide hydrolase activity, while the N-terminal domain exhibits phosphatase activity
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
the enzyme sequence contains 1 putative O-glycosylation and 3 putative N-glycosylation sites
phosphoprotein
the enzyme sequence contains 23 putative phosphorylation sites
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of several crystal structures of apoenzyme and enzyme bound to inhibitor urea for molecular dynamics simulations and determination of active site conformation replacing the inhibitor by substrate trans-methylstyrene oxide in the crystal structure model, minimized structure models
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C154Y
single nucleotide polymorphisms of gene EPHX2, the mutation leads to slightly reduced cell death
K55R
R103C
single nucleotide polymorphisms of gene EPHX2, the mutation leads to slightly reduced cell death
R103C/R287Q
single nucleotide polymorphisms of gene EPHX2, the mutation leads to slightly reduced cell death
R287Q
D335S
-
hydrolase knock-out construct, the mutant enzyme displays only phosphatase activity
D9A
-
phosphatase knock-out construct, the mutant enzyme displays only hydrolase activity
D9A/D335S
-
sEH protein with mutated phosphatase and hydrolase active sites, the mutant is inactive
H237N
-
117.2% of the activity of the wild-type enzyme with trans-stilbene oxide
H431S
-
mutation of His431 results in total loss of activity, the mutant can form the intermediate but cannot hydrolyze it
additional information
K55R
the sEH variant K55R has increased epoxide hydrolase activity and is associated with coronary artery disease
K55R
single nucleotide polymorphisms of gene EPHX2, the mutation leads to slightly reduced cell death
R287Q
the R287Q mutation results in sEH protein with reduced stability and reduced epoxide hydrolase activity, as well as decreased ability of homodimer formation
R287Q
single nucleotide polymorphisms of gene EPHX2, leads to improved tolerance against ischemia in vitro, and inhibition of sEH preserves cardiomyocyte viability, mechanism, overview
additional information
129X1/SvJ x C57BL/6 background with targeted disruption of the Ephx2 gene result in Ephx2-null mice. The gene knockout affects the eicosanoid profiles of the muzants
additional information
-
129X1/SvJ x C57BL/6 background with targeted disruption of the Ephx2 gene result in Ephx2-null mice. The gene knockout affects the eicosanoid profiles of the muzants
additional information
construction of knockout mutants of sEH, phenotypes, overview
additional information
construction of sEH knockout mice, that show no sex differences in cerebral blood flow and ischemic damage in contrast to wild-type female and male mice
additional information
enzyme-deficient male mice show decreased plasma testosterone levels alongside with decreased sperm counts and testicular size, phenotype, overview. Homozygous null mice are viable and fertile and show no phenotype at birth, but progressive depeltion of germ cells in testis. Levels of cholesterol precursors lathosterol and demosterol levels are highly reduced, while stigmasterol and campesterol are unaffected, phenotype, overview
additional information
-
enzyme-deficient male mice show decreased plasma testosterone levels alongside with decreased sperm counts and testicular size, phenotype, overview. Homozygous null mice are viable and fertile and show no phenotype at birth, but progressive depeltion of germ cells in testis. Levels of cholesterol precursors lathosterol and demosterol levels are highly reduced, while stigmasterol and campesterol are unaffected, phenotype, overview
additional information
Ephx2-/- mice, sEH knockout and its inhibition prevent hyperglycemia in diabetes, but also that sEH knockout enhances islet GSIS through the amplifying pathway and decreases islet cell apoptosis in diabetes. sEH knockout increases Ca2+ response to high glucose and KCl plus diazoxide, and it reduces islet cell apoptosis in streptozotocin-treated mice
additional information
generation of a transgenic mouse model, which overexpresses sEH specifically in neurons. Transgenic mice show increased neuron labeling in cortex and hippocampus with little change in labeling of other brain regions. Despite a 3fold increase in sEH activity in the brain, there is no change in arterial pressure. Immunohistochemical examination of transgenic mouse brain regions, overview
additional information
-
generation of a transgenic mouse model, which overexpresses sEH specifically in neurons. Transgenic mice show increased neuron labeling in cortex and hippocampus with little change in labeling of other brain regions. Despite a 3fold increase in sEH activity in the brain, there is no change in arterial pressure. Immunohistochemical examination of transgenic mouse brain regions, overview
additional information
genetic deletion of soluble epoxide hydrolase attenuates the inflammatory response in the femoral cuff model, overview
additional information
male mice lacking the sEH gene had lower systolic blood pressure
additional information
mice lacking sEH have significantly higher circulating EET levels and lower blood pressure compared to wild-type mice, administration of an sEH inhibitor significantly lowers blood pressure in various rodent models of hypertension, and Ephx2 is a susceptibility gene for hypertension-associated heart failure, overview
additional information
soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension
additional information
construction of sEH-/- knockout mice, phenotype compared to wild-type, overview
additional information
-
construction of mutants with point mutations in a wild-type SKI sequence motif, some mutant enzymes show altered subcellular localization, expression in tobacco BY-2 cells results in peroxisomal expression for recombinant wild-type and modified enzymes, overview
additional information
-
mice with targeted disruption of the Ephx2 gene coding for soluble epoxide hydrolase have normal heart anatomy and basal contractile function, but have higher fatty acid epoxide:diol ratios in plasma and cardiomyocytes cell culture media. The heart have improved recovery of left ventricular developed pressure and less infarction after 20 min ischemia, compared with wild-type. Perfusion with 14,15-epoxyeicosa-5(Z)-enoic acid before ischemia abolishes this cardioprotective phenotype. Enzyme null mice exhibit increased cardiac expression of glycogen synthase kinase-3beta phosphoprotein after ischemia
additional information
construction of N-truncated murine EH3 and N-truncated+7aa-insert murine EH3 mutants
additional information
-
construction of N-truncated murine EH3 and N-truncated+7aa-insert murine EH3 mutants
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
-
over 50% loss of activity within 10 min, more than 90% loss of activity within 25 min
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
from hippocampus for enzyme identification by 2D-electrophoresis and MALDI mass spectrometry
from liver by affinity chromatography on an epoxy activated resin derivatized with benzyl thiol
-
to homogeneity from liver by ultracentrifugation, ion exchange, hydrophobic interaction and hydroxyapatite chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
transient expression of wild-type and modified enzymes in HeLa cells, in NIH-3T3 cells, and in tobacco BY-2 cells, the latter via microprojectile bombardment
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of sEH is significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced status epilepticus
high glucose levels suppress sEH expression in diabetic mouse liver, which is reversible by insulin
enzyme expression increases 3-28 days after pilocarpine-induced status epilepticus
-
sEH is synthesized in adipocytes and expression levels increase upon differentiation of 3T3-L1 preadipocytes. Peroxisome proliferator-activated receptor gamma agonists increase the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
sEH is a cross-functional target with the potential for therapeutic utility in the areas of hypertension, inflammation, and organ protection
medicine
medicine
pharmacology
synthesis
-
highly enantioselective synthesis of chiral 1,2 diols from epoxides in ionic liquid [bmim][PF6] or [bmim][Tf2N] in presence of 10% water
medicine
sEH is a target for the treatment of hypertension, inflammatory diseases, pain, diabetes, and stroke
medicine
since the metabolism of EETs by sEH reduces or eliminates their bioactivity, inhibition of sEH has become a therapeutic strategy for hypertension and inflammation
medicine
-
mice with targeted disruption of the Ephx2 gene coding for soluble epoxide hydrolase have normal heart anatomy and basal contractile function, but have higher fatty acid epoxide:diol ratios in plasma and cardiomyocytes cell culture media. The heart have improved recovery of left ventricular developed pressure and less infarction after 20 min ischemia, compared with wild-type. Perfusion with 14,15-epoxyeicosa-5(Z)-enoic acid before ischemia abolishes this cardioprotective phenotype. Enzyme null mice exhibit increased cardiac expression of glycogen synthase kinase-3beta phosphoprotein after ischemia
medicine
-
sEH inhibitors may be useful in the treatment of patients with atherosclerotic cardiovascular disease
medicine
-
soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo and reduce the infarct size
medicine
-
soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy
medicine
-
the activity of sEH plays a significant role in determining the magnitude of acute hypoxic vasoconstriction
medicine
-
modulation of the vascular response mediated through adenosine A2A receptor using aortas from mice fed a 4% NaCl high salt or 0.45% NaCl low salt diet for 4-5 weeks. Compared with NS, HS vessels show increased CYP2J2 and A2A adenosine receptor expression but decreased sEH, CYP4A, and A1 adenosine receptor expression. Data suggest that in mice fed low salt containing diet, upregulation of arterial A1 receptor causes vasoconstriction via increased sEH and CYP4A proteins. In mice fed high salt-containing diet, upregulation of A2A receptor protein triggers vascular relaxation through ATP-sensitive channels via upregulation of CYP2J2 enzyme
medicine
-
sEH is synthesized in adipocytes and expression levels increase upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels do not differ in the fat pads from mice receiving a regular or a high-fat diet, total adipose sEH activity is higher in the obese mice. Peroxisome proliferator-activated receptor gamma agonists increase the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo
medicine
-
study on the mechanism behind adenosine-induced vascular response in high salt-fed eNOS+/+ and eNOS-/- mice. Compared to low salt diet, high salt diet increases CYP2J2 in eNOS+/+ and eNOS-/- mice, but decreases sEH in eNOS+/+ and eNOS-/- animals. Similarly, CYP4A decreases in high salt-fed-eNOS+/+ and -eNOS-/- animals. Data suggest that low salt diet causes reduced-vasodilation in both eNOS+/+ and eNOS-/- background via sEH and CYP4A
medicine
-
brain microvascular endothelial cells from female brain are more resistant to ischemic injury compared to male cells due to lower expression of soluble epoxide hydrolase
medicine
-
treatment with soluble epoxide hydrolase inhibitors can reduce acute kidney injury
pharmacology
-
the enzyme is a key target in treatment of acute systemic hypotension
pharmacology
-
the enzyme is a target for inhibition in therapy of disorders resulting from hypertension and vascular inflammation
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wixtrom, R.N.; Hammock, B.D.
Membrane-bound and soluble-fraction epoxide hydrolases
Biochem. Pharmacol. Toxicol.
1
1-93
1985
Oryctolagus cuniculus, Homo sapiens, Macaca mulatta, Mus musculus, Rattus norvegicus
-
Ota, K.; Hammock, B.D.
Cytosolic and microsomal epoxide hydrolases: differential properties in mammalian liver
Science
207
1479-1481
1980
Cavia porcellus, Mus musculus, Rattus norvegicus
Gill, S.S.
Purification of mouse liver cytosolic epoxide hydrolase
Biochem. Biophys. Res. Commun.
112
763-769
1983
Mus musculus
Meijer, J.; Depierre, J.W.
Properties of cytosolic epoxide hydrolase purified from the liver of untreated and clofibrate-treated mice. Purification procedure and physiochemical characterization of the pure enzymes
Eur. J. Biochem.
148
421-430
1985
Mus musculus
Prestwich, G.D.; Hammock, B.D.
Rapid purification of cytosolic epoxide hydrolase from normal and clofibrate-treated animals by affinity chromatography
Proc. Natl. Acad. Sci. USA
82
1663-1667
1985
Mus musculus
Meijer, J.; Depierre, J.W.
Properties of cytosolic epoxide hydrolase purified from the liver of untreated and clofibrate-treated mice. Characterization of optimal assay conditions, substrate specificity and effects of modulators on the catalytic activity
Eur. J. Biochem.
150
7-16
1985
Mus musculus
Hammock, B.D.; Prestwich, G.D.; Loury, D.N.; Cheung, P.Y.K.; Eng, W.S.; Park, S.K.; Moody, D.E.; Silva, M.H.; Wixtrom, R.N.
Comparison of crude and affinity purified cytosolic epoxide hydrolases from hepatic tissue of control and clofibrate-fed mice
Arch. Biochem. Biophys.
244
292-309
1986
Mus musculus
Meijer, J.; DePierre, J.W.
Cytosolic epoxide hydrolase
Chem. Biol. Interact.
64
207-249
1988
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus
Wixtrom, R.N.; Silva, M.H.; Hammock, B.D.
Affinity purification of cytosolic epoxide hydrolase using derivatized epoxy-activated Sepharose gels
Anal. Biochem.
169
71-80
1988
Mus musculus
Pinot, F.; Grant, D.F.; Beetham, J.K.; Parker, A.G.; Borhan, B.; Landt, S.; Jones, A.D.; Hammock, B.D.
Molecular and biochemical evidence for the involvement of the Asp-333-His-523 pair in the catalytic mechanism of soluble epoxide hydrolase
J. Biol. Chem.
270
7968-7974
1995
Mus musculus
Chang, C.; Gill, S.S.
Purification and characterization of an epoxide hydrolase from the peroxisomal fraction of mouse liver
Arch. Biochem. Biophys.
285
276-284
1991
Mus musculus
Halarnkar, P.P.; Nourooz-Zadeh, J.; Kuwano, E.; Jones, A.D.; Hammock, B.D.
Formation of cyclic products from the diepoxide of long-chain fatty esters by cytosolic epoxide hydrolase
Arch. Biochem. Biophys.
294
586-593
1992
Mus musculus
Nourooz-Zadeh, J.; Winder, B.S.; Dietze, E.C.; Giometti, C.S.; Tollaksen, S.L.; Hammock, B.D.
Biochemical characterization of a variant form of cytosolic epoxide hydrolase induced by parental exposure to N-ethyl-N-nitrosurea
Comp. Biochem. Physiol. C
103
207-214
1992
Mus musculus, Mus musculus ENU4
Dietze, E.C.; Magdalou, J.; Hammock, B.D.
Human and murine cytosolic epoxide hydrolase: Physical and structural properties
Int. J. Biochem.
22
461-470
1990
Homo sapiens, Mus musculus
Morisseau, C.; Beetham, J.K.; Pinot, F.; Debernard, S.; Newman, J.W.; Hammock, B.D.
Cress and potato soluble epoxide hydrolases: purification, biochemical characterization, and comparison to mammalian enzymes
Arch. Biochem. Biophys.
378
321-332
2000
Arabidopsis thaliana, cress, Homo sapiens, Mus musculus, Rattus norvegicus, Solanum tuberosum
Shin, J.H.; Engidawork, E.; Delabar, J.M.; Lubec, G.
Identification and characterization of soluble epoxide hydrolase in mouse brain by a robust protein biocehmical method
Amino Acids
28
63-69
2005
Mus musculus (P34914), Mus musculus
Jones, P.D.; Wolf, N.M.; Morisseau, C.; Whetstone, P.; Hock, B.; Hammock, B.D.
Fluorescent substrates for soluble epoxide hydrolase and application to inhibition studies
Anal. Biochem.
343
66-75
2005
Homo sapiens, Mus musculus
Morisseau, C.; Hammock, B.D.
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles
Annu. Rev. Pharmacol. Toxicol.
45
311-333
2005
Homo sapiens, Mus musculus, Rattus norvegicus
Morisseau, C.; Du, G.; Newman, J.W.; Hammock, B.D.
Mechanism of mammalian soluble epoxide hydrolase inhibition by chalcone oxide derivatives
Arch. Biochem. Biophys.
356
214-228
1998
Homo sapiens, Mus musculus
Dietze, E.C.; Kuwano, E.; Casa, J.; Hammock, B.D.
Inhibition of cytosolic epoxide hydrolase by trans-3-phenylglycidols
Biochem. Pharmacol.
42
1163-1175
1991
Mus musculus
Dietze, E.C.; Stephens, J.; Magdalou, J.; Bender, D.M.; Moyer, M.; Fowler, B.; Hammock, B.D.
Inhibition of human and murine cytosolic epoxide hydrolase by group-selective reagents
Comp. Biochem. Physiol. B
104
299-308
1993
Homo sapiens, Mus musculus
Mullen, R.T.; Trelease, R.N.; Duerk, H.; Arand.M.; Hammock, B.D.; Oesch, F.; Grant, D.F.
Differential subcellular localization of endogenous and transfected soluble epoxide hydrolase in mammalian cells: evidence for isozyme variants
FEBS Lett.
445
301-305
1999
Mus musculus, Rattus norvegicus
Dietze, E.D.; Kuwano, E.; Hammock, B.D.
The interaction of cytosolic epoxide hydrolase with chiral epoxides
Int. J. Biochem.
25
43-52
1993
Mus musculus
Schiott, B.; Bruice, T.C.
Reaction mechanism of soluble epoxide hydrolase: insights from molecular dynamics simulations
J. Am. Chem. Soc.
124
14558-14570
2002
Mus musculus (P34914)
Haeggstroem, J.; Meijer, J.; Radmark, O.
Leukotriene A4. Enzymatic conversion into 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid by mouse liver cytosolic epoxide hydrolase
J. Biol. Chem.
261
6332-6337
1986
Mus musculus
McElroy, N.R.; Jurs, P.C.
QSAR and classification of murine and human soluble epoxide hydrolase inhibition by urea-like compounds
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46
1066-1080
2003
Homo sapiens, Mus musculus
Cronin, A.; Mowbray, S.; Duerk, H.; Homburg, S.; Fleming, I.; Fisslthaler, B.; Oesch, F.; Arand, M.
The N-terminal domain of mammalian soluble epoxide hydrolase is a phosphatase
Proc. Natl. Acad. Sci. USA
100
1552-1557
2003
Homo sapiens, Rattus norvegicus, Mus musculus (P34914)
Schmelzer, K.R.; Kubala, L.; Newman, J.W.; Kim, I.H.; Eiserich, J.P.; Hammock, B.D.
Soluble epoxide hydrolase is a therapeutic target for acute inflammation
Proc. Natl. Acad. Sci. USA
102
9772-9777
2005
Mus musculus
Newman, J.W.; Morisseau, C.; Hammock, B.D.
Epoxide hydrolases: their roles and interactions with lipid metabolism
Prog. Lipid Res.
44
1-51
2005
Ananas comosus, Apium graveolens, Arabidopsis thaliana, Papio sp., Brassica napus, Ricinus communis, Cavia porcellus, Oryctolagus cuniculus, Equus caballus, Euphorbia lagascae, Glycine max, Homo sapiens, Macaca mulatta, Oryzias latipes, Mesocricetus auratus, Nicotiana tabacum, Oncorhynchus mykiss, Oryza sativa, Rattus norvegicus, Solanum tuberosum, Spinacia oleracea, Sus scrofa, Triticum aestivum, Vicia sativa, Zea mays, Citrus jambhiri, Malus pumila, Pimephales promelas, Stenotomus chrysops, Mus musculus (P34914)
Draper, A.J.; Hammock, B.D.
Inhibition of soluble and microsomal epoxide hydrolase by zinc and other metals
Toxicol. Sci.
52
26-32
1999
Homo sapiens, Mus musculus, Rattus norvegicus, Solanum tuberosum
Seubert, J.M.; Sinal, C.J.; Graves, J.; DeGraff, L.M.; Bradbury, J.A.; Lee, C.R.; Goralski, K.; Carey, M.A.; Luria, A.; Newman, J.W.; Hammock, B.D.; Falck, J.R.; Roberts, H.; Rockman, H.A.; Murphy, E.; Zeldin, D.C.
Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function
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99
442-450
2006
Mus musculus
Chiappe, C.; Leandri, E.; Hammock, B.D.; Morisseau, C.
Effect of ionic liquids on epoxide hydrolase-catalyzed synthesis of chiral 1,2-diols
Green Chem.
9
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2007
Mus musculus
Hwang, S.H.; Tsai, H.J.; Liu, J.Y.; Morisseau, C.; Hammock, B.D.
Orally bioavailable potent soluble epoxide hydrolase inhibitors
J. Med. Chem.
50
3825-3840
2007
Canis lupus, Felis catus, Mesocricetus auratus, Mus musculus, Rattus norvegicus, Homo sapiens (P34913), Homo sapiens
Motoki, A.; Merkel, M.J.; Packwood, W.H.; Cao, Z.; Liu, L.; Iliff, J.; Alkayed, N.J.; Van Winkle, D.M.
Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo
Am. J. Physiol. Heart Circ. Physiol.
295
H2128-H2134
2008
Mus musculus
Decker, M.; Arand, M.; Cronin, A.
Mammalian epoxide hydrolases in xenobiotic metabolism and signalling
Arch. Toxicol.
83
297-318
2009
Homo sapiens, Mus musculus (P34914)
Liu, J.Y.; Tsai, H.J.; Hwang, S.H.; Jones, P.D.; Morisseau, C.; Hammock, B.D.
Pharmacokinetic optimization of four soluble epoxide hydrolase inhibitors for use in a murine model of inflammation
Br. J. Pharmacol.
156
284-296
2009
Homo sapiens, Mus musculus, Rattus norvegicus
Parrish, A.R.; Chen, G.; Burghardt, R.C.; Watanabe, T.; Morisseau, C.; Hammock, B.D.
Attenuation of cisplatin nephrotoxicity by inhibition of soluble epoxide hydrolase
Cell Biol. Toxicol.
25
217-225
2009
Mus musculus
Gross, G.J.; Nithipatikom, K.
Soluble epoxide hydrolase: a new target for cardioprotection
Curr. Opin. Investig. Drugs
10
253-258
2009
Mus musculus, Rattus norvegicus
Keserue, B.; Barbosa-Sicard, E.; Popp, R.; Fisslthaler, B.; Dietrich, A.; Gudermann, T.; Hammock, B.D.; Falck, J.R.; Weissmann, N.; Busse, R.; Fleming, I.
Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response
FASEB J.
22
4306-4315
2008
Mus musculus
EnayetAllah, A.E.; Luria, A.; Luo, B.; Tsai, H.J.; Sura, P.; Hammock, B.D.; Grant, D.F.
Opposite regulation of cholesterol levels by the phosphatase and hydrolase domains of soluble epoxide hydrolase
J. Biol. Chem.
283
36592-36598
2008
Homo sapiens, Mus musculus
Ulu, A.; Davis, B.B.; Tsai, H.J.; Kim, I.H.; Morisseau, C.; Inceoglu, B.; Fiehn, O.; Hammock, B.D.; Weiss, R.H.
Soluble epoxide hydrolase inhibitors reduce the development of atherosclerosis in apolipoprotein e-knockout mouse model
J. Cardiovasc. Pharmacol.
52
314-323
2008
Homo sapiens, Mus musculus
Fife, K.L.; Liu, Y.; Schmelzer, K.R.; Tsai, H.J.; Kim, I.H.; Morisseau, C.; Hammock, B.D.; Kroetz, D.L.
Inhibition of soluble epoxide hydrolase does not protect against endotoxin-mediated hepatic inflammation
J. Pharmacol. Exp. Ther.
327
707-715
2008
Mus musculus
Ai, D.; Pang, W.; Li, N.; Xu, M.; Jones, P.D.; Yang, J.; Zhang, Y.; Chiamvimonvat, N.; Shyy, J.Y.; Hammock, B.D.; Zhu, Y.
Soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy
Proc. Natl. Acad. Sci. USA
106
564-569
2009
Mus musculus, Rattus norvegicus
Luria, A.; Morisseau, C.; Tsai, H.J.; Yang, J.; Inceoglu, B.; De Taeye, B.; Watkins, S.M.; Wiest, M.M.; German, J.B.; Hammock, B.D.
Alteration in plasma testosterone levels in male mice lacking soluble epoxide hydrolase
Am. J. Physiol. Endocrinol. Metab.
297
E375-E383
2009
Mus musculus (P34914), Mus musculus
Merkel, M.J.; Liu, L.; Cao, Z.; Packwood, W.; Young, J.; Alkayed, N.J.; Van Winkle, D.M.
Inhibition of soluble epoxide hydrolase preserves cardiomyocytes: role of STAT3 signaling
Am. J. Physiol. Heart Circ. Physiol.
298
H679-H687
2010
Mus musculus (P34914)
Manhiani, M.; Quigley, J.E.; Knight, S.F.; Tasoobshirazi, S.; Moore, T.; Brands, M.W.; Hammock, B.D.; Imig, J.D.
Soluble epoxide hydrolase gene deletion attenuates renal injury and inflammation with DOCA-salt hypertension
Am. J. Physiol. Renal Physiol.
297
F740-F748
2009
Mus musculus (P34914)
Zhang, L.N.; Vincelette, J.; Cheng, Y.; Mehra, U.; Chen, D.; Anandan, S.K.; Gless, R.; Webb, H.K.; Wang, Y.X.
Inhibition of soluble epoxide hydrolase attenuated atherosclerosis, abdominal aortic aneurysm formation, and dyslipidemia
Arterioscler. Thromb. Vasc. Biol.
29
1265-1270
2009
Mus musculus (P34914), Mus musculus
Revermann, M.; Schloss, M.; Barbosa-Sicard, E.; Mieth, A.; Liebner, S.; Morisseau, C.; Geisslinger, G.; Schermuly, R.T.; Fleming, I.; Hammock, B.D.; Brandes, R.P.
Soluble epoxide hydrolase deficiency attenuates neointima formation in the femoral cuff model of hyperlipidemic mice
Arterioscler. Thromb. Vasc. Biol.
30
909-914
2010
Mus musculus (P34914)
Liu, J.Y.; Yang, J.; Inceoglu, B.; Qiu, H.; Ulu, A.; Hwang, S.H.; Chiamvimonvat, N.; Hammock, B.D.
Inhibition of soluble epoxide hydrolase enhances the anti-inflammatory effects of aspirin and 5-lipoxygenase activation protein inhibitor in a murine model
Biochem. Pharmacol.
79
880-887
2010
Mus musculus (P34914), Mus musculus
Mavrommatis, Y.; Ross, K.; Rucklidge, G.; Reid, M.; Duncan, G.; Gordon, M.J.; Thies, F.; Sneddon, A.; de Roos, B.
Intervention with fish oil, but not with docosahexaenoic acid, results in lower levels of hepatic soluble epoxide hydrolase with time in apoE knockout mice
Br. J. Nutr.
103
16-24
2010
Mus musculus (P34914)
Bianco, R.A.; Agassandian, K.; Cassell, M.D.; Spector, A.A.; Sigmund, C.D.
Characterization of transgenic mice with neuron-specific expression of soluble epoxide hydrolase
Brain Res.
1291
60-72
2009
Mus musculus (P34914), Mus musculus
Keserue, B.; Barbosa-Sicard, E.; Schermuly, R.T.; Tanaka, H.; Hammock, B.D.; Weissmann, N.; Fisslthaler, B.; Fleming, I.
Hypoxia-induced pulmonary hypertension: comparison of soluble epoxide hydrolase deletion vs. inhibition
Cardiovasc. Res.
85
232-240
2010
Homo sapiens (P34913), Homo sapiens, Mus musculus (P34914), Mus musculus C57BL/6 (P34914)
Qiu, H.; Li, N.; Liu, J.Y.; Harris, T.R.; Hammock, B.D.; Chiamvimonvat, N.
Soluble epoxide hydrolase inhibitors and heart failure
Cardiovasc. Ther.
29
99-111
2011
Homo sapiens, Mus musculus (P34914)
Wang, Y.X.; Ulu, A.; Zhang, L.N.; Hammock, B.
Soluble epoxide hydrolase in atherosclerosis
Curr. Atheroscler. Rep.
12
174-183
2010
Homo sapiens (P34913), Homo sapiens, Mus musculus (P34914), Rattus norvegicus (P80299)
Marino, J.P.
Soluble epoxide hydrolase, a target with multiple opportunities for cardiovascular drug discovery
Curr. Top. Med. Chem.
9
452-463
2009
Mus musculus (P34914)
Oguro, A.; Fujita, N.; Imaoka, S.
Regulation of soluble epoxide hydrolase (sEH) in mice with diabetes: high glucose suppresses sEH expression
Drug Metab. Pharmacokinet.
24
438-445
2009
Homo sapiens, Mus musculus (P34914)
Iliff, J.J.; Alkayed, N.J.
Soluble epoxide hydrolase inhibition: targeting multiple mechanisms of ischemic brain injury with a single agent
Future Neurol.
4
179-199
2009
Homo sapiens (P34913), Mus musculus (P34914), Rattus norvegicus (P80299)
Barbosa-Sicard, E.; Froemel, T.; Keserue, B.; Brandes, R.P.; Morisseau, C.; Hammock, B.D.; Braun, T.; Krueger, M.; Fleming, I.
Inhibition of the soluble epoxide hydrolase by tyrosine nitration
J. Biol. Chem.
284
28156-28163
2009
Homo sapiens (P34913), Homo sapiens, Mus musculus (P34914), Mus musculus, Mus musculus C57BL/6 (P34914)
Chaudhary, K.R.; Abukhashim, M.; Hwang, S.H.; Hammock, B.D.; Seubert, J.M.
Inhibition of soluble epoxide hydrolase by trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid is protective against ischemia-reperfusion injury
J. Cardiovasc. Pharmacol.
55
67-73
2010
Mus musculus (P34914), Mus musculus C57BL6 (P34914)
Zhang, W.; Iliff, J.J.; Campbell, C.J.; Wang, R.K.; Hurn, P.D.; Alkayed, N.J.
Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia
J. Cereb. Blood Flow Metab.
29
1475-1481
2009
Mus musculus (P34914)
Li, N.; Liu, J.Y.; Timofeyev, V.; Qiu, H.; Hwang, S.H.; Tuteja, D.; Lu, L.; Yang, J.; Mochida, H.; Low, R.; Hammock, B.D.; Chiamvimonvat, N.
Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches
J. Mol. Cell. Cardiol.
47
835-845
2009
Mus musculus (P34914), Mus musculus
Deng, Y.; Theken, K.N.; Lee, C.R.
Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation
J. Mol. Cell. Cardiol.
48
331-341
2010
Homo sapiens (P34913), Mus musculus (P34914)
Luo, P.; Chang, H.H.; Zhou, Y.; Zhang, S.; Hwang, S.H.; Morisseau, C.; Wang, C.Y.; Inscho, E.W.; Hammock, B.D.; Wang, M.H.
Inhibition or deletion of soluble epoxide hydrolase prevents hyperglycemia, promotes insulin secretion, and reduces islet apoptosis
J. Pharmacol. Exp. Ther.
334
430-438
2010
Mus musculus (P34914), Mus musculus C57/BL6J (P34914)
Marowsky, A.; Burgener, J.; Falck, J.R.; Fritschy, J.M.; Arand, M.
Distribution of soluble and microsomal epoxide hydrolase in the mouse brain and its contribution to cerebral epoxyeicosatrienoic acid metabolism
Neuroscience
163
646-661
2009
Mus musculus (P34914), Mus musculus, Mus musculus C57BL/6 (P34914)
Nayeem, M.A.; Zeldin, D.C.; Boegehold, M.A.; Morisseau, C.; Marowsky, A.; Ponnoth, D.S.; Roush, K.P.; Falck, J.R.
Modulation by salt intake of the vascular response mediated through adenosine A(2A) receptor: role of CYP epoxygenase and soluble epoxide hydrolase
Am. J. Physiol. Regul. Integr. Comp. Physiol.
299
R325-R333
2010
Mus musculus
Cronin, A.; Decker, M.; Arand, M.
Mammalian soluble epoxide hydrolase is identical to liver hepoxilin hydrolase
J. Lipid Res.
52
712-719
2011
Homo sapiens, Mus musculus, Rattus norvegicus
Hwang, S.H.; Wagner, K.M.; Morisseau, C.; Liu, J.Y.; Dong, H.; Wecksler, A.T.; Hammock, B.D.
Synthesis and structure-activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase
J. Med. Chem.
54
3037-3050
2011
Mus musculus, Homo sapiens (P34913)
Nayeem, M.A.; Zeldin, D.C.; Boegehold, M.A.; Falck, J.R.
Salt modulates vascular response through adenosine A(2A) receptor in eNOS-null mice: role of CYP450 epoxygenase and soluble epoxide hydrolase
Mol. Cell. Biochem.
350
101-111
2011
Mus musculus
De Taeye, B.; Morisseau, C.; Coyle, J.; Covington, J.; Luria, A.; Yang, J.; Murphy, S.; Friedman, D.; Hammock, B.; Vaughan, D.
Expression and regulation of soluble epoxide hydrolase in adipose tissue
Obesity (Silver Spring)
18
489-498
2010
Mus musculus
Sun, D.; Cuevas, A.J.; Gotlinger, K.; Hwang, S.H.; Hammock, B.D.; Schwartzman, M.L.; Huang, A.
Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure
Am. J. Physiol. Heart Circ. Physiol.
306
H1146-H1153
2014
Mus musculus
Gupta, N.C.; Davis, C.M.; Nelson, J.W.; Young, J.M.; Alkayed, N.J.
Soluble epoxide hydrolase: sex differences and role in endothelial cell survival
Arterioscler. Thromb. Vasc. Biol.
32
1936-1942
2012
Mus musculus
Lonsdale, R.; Hoyle, S.; Grey, D.T.; Ridder, L.; Mulholland, A.J.
Determinants of reactivity and selectivity in soluble epoxide hydrolase from quantum mechanics/molecular mechanics modeling
Biochemistry
51
1774-1786
2012
Mus musculus (P34914)
Hung, Y.W.; Hung, S.W.; Wu, Y.C.; Wong, L.K.; Lai, M.T.; Shih, Y.H.; Lee, T.S.; Lin, Y.Y.
Soluble epoxide hydrolase activity regulates inflammatory responses and seizure generation in two mouse models of temporal lobe epilepsy
Brain Behav. Immun.
43
118-129
2015
Mus musculus
Lee, J.P.; Yang, S.H.; Lee, H.Y.; Kim, B.; Cho, J.Y.; Paik, J.H.; Oh, Y.J.; Kim, D.K.; Lim, C.S.; Kim, Y.S.
Soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney
PLoS ONE
7
e37075
2012
Mus musculus
Liu, J.Y.; Tsai, H.J.; Morisseau, C.; Lango, J.; Hwang, S.H.; Watanabe, T.; Kim, I.H.; Hammock, B.D.
In vitro and in vivo metabolism of N-adamantyl substituted urea-based soluble epoxide hydrolase inhibitors
Biochem. Pharmacol.
98
718-731
2015
Homo sapiens (P34913), Homo sapiens, Mus musculus (P34914), Rattus norvegicus (P80299), Mus musculus C57BL/6 (P34914), Rattus norvegicus Sprague Dawley (P80299)
Burmistrov, V.; Morisseau, C.; Harris, T.R.; Butov, G.; Hammock, B.D.
Effects of adamantane alterations on soluble epoxide hydrolase inhibition potency, physical properties and metabolic stability
Bioorg. Chem.
76
510-527
2018
Homo sapiens (P34913), Homo sapiens, Mus musculus (P34914), Mus musculus, Rattus norvegicus (P80299)
Hung, Y.; Hung, S.; Wu, Y.; Wong, L.; Lai, M.; Shih, Y.; Lee, T.; Lin, Y.
Soluble epoxide hydrolase activity regulates inflammatory responses and seizure generation in two mouse models of temporal lobe epilepsy
Brain Behav. Immun.
43
118-129
2015
Mus musculus (P34914), Mus musculus, Mus musculus C57BL/6 (P34914)
Yamanashi, H.; Boeglin, W.E.; Morisseau, C.; Davis, R.W.; Sulikowski, G.A.; Hammock, B.D.; Brash, A.R.
Catalytic activities of mammalian epoxide hydrolases with cis and trans fatty acid epoxides relevant to skin barrier function
J. Lipid Res.
59
684-695
2018
Homo sapiens (P34913), Homo sapiens (Q9H6B9), Homo sapiens, Mus musculus (Q3V1F8), Mus musculus
Mangels, N.; Awwad, K.; Wettenmann, A.; Dos Santos, L.R.; Froemel, T.; Fleming, I.
The soluble epoxide hydrolase determines cholesterol homeostasis by regulating AMPK and SREBP activity
Prostaglandins Other Lipid Mediat.
125
30-39
2016
Mus musculus (P34914), Mus musculus C57BL/6 (P34914)
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