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Information on EC 3.3.2.10 - soluble epoxide hydrolase and Organism(s) Rattus norvegicus and UniProt Accession P80299
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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: Rattus norvegicus
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
additional information
-
the enzyme belongs to the alpha/beta-hydrolase fold family of proteins
additional information
-
the enzyme belongs to the family of C-X bond hydrolase enzymes
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
two step mechanism with formation of of a hydroxyl-alkyl-enzyme intermediate, the catalytic triad is Asp333-His523-Asp495, catalytic cycle
-
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
(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
-
-
-
?
trans-diphenyl-propene oxide + H2O
trans-diphenyl-propene diol
-
-
-
?
(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
-
-
?
1,3-trans-diphenylpropene oxide + H2O
1,3-diphenylpropane-1,2-diol
-
sEH-selective substrate
-
-
?
11,12-epoxyeicosatrienoic acid + H2O
11,12-dihydroxyeicosatrienoic acid
-
-
-
-
?
14,15-epoxyeicosatrienoic acid + H2O
14,15-dihydroxyeicosatrienoic acid
-
-
-
-
?
3-phenyl-oxiranyl-acetic acid cyano-(6-methoxy-naphthalen-2-yl)-methyl ester + H2O
?
-
-
-
-
?
4-nitrophenyl (2R,3R)-2,3-epoxy-3-phenylpropyl carbonate + H2O
?
-
5.1% of the activity with 2,3-epoxy-1,3-diphenyl-propane, no activity with the 2S,3S-enantiomer
-
-
?
5,6-epoxyeicosatrienoic acid + H2O
5,6-dihydroxyeicosatrienoic acid
-
-
-
-
?
8,9-epoxyeicosatrienoic acid + H2O
8,9-dihydroxyeicosatrienoic acid
-
-
-
-
?
benzopyrene 4,5-oxide + H2O
(-)benzopyrene 4,5-dihydrodiol
-
-
-
-
?
cis-(9R,10S)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
-
enantioselective, low production rate of the (9R,10R)-diol by wild-type and E404D mutant
-
?
cis-(9S,10R)-epoxystearic acid + H2O
threo-(9R,10R)-dihydroxystearic acid + threo-(9S,10S)-dihydroxystearic acid
-
-
enantioselective, low production rate of the (9R,10R)-diol by wild-type and E404D mutant
-
?
cis-1,3-diphenylpropene oxide + H2O
1,3-diphenylpropane-1,2-diol
-
2.1% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
cis-9,10-epoxy-12-octadecenoate methyl ester + H2O
9,10-dihydroxystearic acid methyl ester
-
3.5% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
cis-9,10-epoxystearic acid + H2O
9,10-dihydroxystearic acid
-
4.1% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
cyano(2-methoxynaphthalen-6-yl)methyl(3-phenyloxiran-2-yl)methyl carbonate + H2O
?
-
-
-
-
?
juvenile hormone III + H2O
?
-
3.5% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
trans-stilbene oxide + H2O
1,2-diphenylethane-1,2-diol
-
highly selective for the trans-enantiomer. 1% of the activity with 2,3-epoxy-1,3-diphenyl-propane
-
-
?
trans-stilbene oxide + H2O
?
-
-
-
-
?
(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
EETs 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
-
-
?
(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
-
-
?
epoxyeicosatrienoic acid + H2O
dihydroxyeicosatrienoic acid
-
physiological function and regulation of the reaction, overview
-
-
?
additional information
?
-
SEH converts cardiovascular protective epoxyeicosatrienoic acids into less active diols attenuating the protective properties, overview
-
-
?
additional information
?
-
-
Asp333, Asp495 and His523 form the catalytic triad
-
-
?
additional information
?
-
-
enzyme inhibition in vivo leads to increased blood pressure and heart rate due to an increase in epoxyeicosatrienoic acid-mediated generation of reactive oxygen species
-
-
?
additional information
?
-
-
the activity for epoxyeicosatrienoic acids is elevated 5 to 54fold in renal cortical S9 fraction from the spontaneously hypertensive rats compared to normotensive Wistar-Kyoto rats, the enzyme is involved in regulation of blood pressure
-
-
?
additional information
?
-
-
the enzyme is involved in metabolism of epoxide lipids in blood pressure, inflammation, reproduction and in lidpi/carbohydrate metabolism, enzyme regulation, overview
-
-
?
additional information
?
-
-
the enzyme is involved in regulation of blood pressure and inflammation
-
-
?
additional information
?
-
-
the enzyme is involved in the arachidonic acid metabolic pathway
-
-
?
additional information
?
-
-
enantioselectivity with fatty acid epoxide substrates
-
-
?
additional information
?
-
-
sEH prefers gem-di-, trans-di-, cis-di-, tri-, and tetra-substituted epoxides
-
-
?
additional information
?
-
-
substrate specificity, no activity with benz[a]pyrene 4,5-oxide
-
-
?
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 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, overview
-
-
?
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
-
-
-
-
?
epoxyeicosatrienoic acid + H2O
dihydroxyeicosatrienoic acid
-
physiological function and regulation of the reaction, overview
-
-
?
(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
EETs 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
-
-
?
(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
-
-
?
additional information
?
-
SEH converts cardiovascular protective epoxyeicosatrienoic acids into less active diols attenuating the protective properties, overview
-
-
?
additional information
?
-
-
enzyme inhibition in vivo leads to increased blood pressure and heart rate due to an increase in epoxyeicosatrienoic acid-mediated generation of reactive oxygen species
-
-
?
additional information
?
-
-
the activity for epoxyeicosatrienoic acids is elevated 5 to 54fold in renal cortical S9 fraction from the spontaneously hypertensive rats compared to normotensive Wistar-Kyoto rats, the enzyme is involved in regulation of blood pressure
-
-
?
additional information
?
-
-
the enzyme is involved in metabolism of epoxide lipids in blood pressure, inflammation, reproduction and in lidpi/carbohydrate metabolism, enzyme regulation, overview
-
-
?
additional information
?
-
-
the enzyme is involved in regulation of blood pressure and inflammation
-
-
?
additional information
?
-
-
the enzyme is involved in the arachidonic acid metabolic pathway
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
no effect on activity by 1 mM Mg2+, Ca2+, and Ba2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3R)-N-[(1s,2R,3S)-2,3-diphenylcyclopropyl]-3-[(4-fluorobenzene-1-sulfonyl)amino]piperidine-1-carboxamide
-
(3R)-N-[(1s,2R,3S)-2,3-diphenylcyclopropyl]-3-[(methanesulfonyl)amino]piperidine-1-carboxamide
-
(R)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
-
(R)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
-
(S)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
-
(S)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
-
1-(1-acetypiperidin-4-yl)-3-adamantanylurea
APAU, a tight binding inhibitor of enzyme sEH
1-(1-nicotinoylpiperidin-4-yl)-3-(4-(trifluoromethoxy) phenyl) urea
i.e. AR9276
1-(3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl)-3-phenylpropan-1-one
-
1-(4-trifluoro-methoxy-phenyl)-3-(1-propionylpiperidin-4-yl)urea
TPPU, a tight binding inhibitor of enzyme sEH
1-[[4-(trifluoromethoxy)phenyl]carbamoyl]piperidine-4-carboxylic acid
-
12-(3-adamantyl-ureido)-dodecanoic acid
AUDA, a tight binding inhibitor of enzyme sEH
2-(2,4-dichlorophenyl)-1-[6-(methylsulfonyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl]ethanone
-
2-(hydroxymethyl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-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
-
3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl[4-(trifluoromethyl)phenyl]methanone
-
3-(3-amino-3-oxopropyl)-N-(4-chlorophenyl)-3-phenylpiperidine-1-carboxamide
-
3-(hydroxymethyl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
-
3-([[(adamantan-1-yl)methyl]carbamoyl]amino)adamantan-1-yl trifluoroacetate
-
3-methyl-3-phenyl-N-(4-(pyridin-3-yl)benzyl)piperidine-1-carboxamide
-
3-methyl-3-phenyl-N-[3-(pyridin-3-yl)propyl]piperidine-1-carboxamide
-
3-methyl-3-phenyl-N-[3-[(1S,2S)-2-phenylcyclopropyl]benzyl]piperidine-1-carboxamide
-
3-methyl-3-phenyl-N-[3-[2-(quinoxalin-6-yl)ethyl]benzyl]piperidine-1-carboxamide
-
3-methyl-3-phenyl-N-[[2'-(trifluoromethyl)biphenyl-4-yl]methyl]piperidine-1-carboxamide
-
3-[1-[(4-chlorophenyl)carbamoyl]-3-(pyridin-2-yl)piperidin-3-yl]propanoic acid
-
3-[1-[(4-chlorophenyl)carbamoyl]-3-(pyridin-3-yl)piperidin-3-yl]propanoic acid
-
3-[1-[(4-chlorophenyl)carbamoyl]-3-(pyridin-4-yl)piperidin-3-yl]propanoic acid
-
3-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]propanoic acid
-
3-[1-[(4-chlorophenyl)carbamoyl]-3-[3-(trifluoromethyl)phenyl]piperidin-3-yl]propanoic acid
-
3-[1-[(4-chlorophenyl)carbamoyl]-3-[4-(trifluoromethyl)phenyl]piperidin-3-yl]propanoic acid
-
3-[3-(biphenyl-4-yl)-1-[(4-chlorophenyl)carbamoyl]piperidin-3-yl]propanoic acid
-
3-[4-[(1-[[(1R,3S)-2,2-dimethyl-3-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
-
3-[4-[(1-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
-
3-[4-[(1-[[(1S,2R,3R)-2-methyl-3-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
-
3-[4-[(1-[[(1s,2R,3S)-2,3-bis(4-fluorophenyl)cyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
-
3-[4-[(1-[[(1s,2R,3S)-2,3-diphenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
-
3-[4-[(1-[[(1S,2S,3R)-2-methyl-3-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
-
4'-hydroxy-N-(2-phenylcyclopropyl)-3',4'-dihydro-1H-spiro[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxamide
-
4-(1H-pyrrol-1-yl)-N-[4-(trifluoromethoxy)phenyl]-piperidinecarboxamide
-
4-(1H-pyrrol-1-yl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
-
4-(4-chlorophenoxy)-N-(2,4-dichlorobenzyl)piperidine-1-carboxamide
-
4-(hydroxymethyl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
-
4-([1-[(2,4-dichlorobenzyl)carbamoyl]piperidin-4-yl]oxy)benzoic acid
-
4-oxo-N-(1,2,3,4-tetrahydronaphthalen-2-yl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
4-oxo-N-(2-phenylcyclopropyl)-6-(pyridin-4-yl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
4-oxo-N-(3-phenylcyclopentyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
4-oxo-N-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
4-oxo-N-[(1S,2R)-2-phenylcyclopropyl]-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
4-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]butanoic 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
-
5-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]pentanoic acid
-
6'-(methylsulfonyl)-N-(2-phenylcyclopropyl)-1H,4'H-spiro[azepane-4,3'-chromene]-1-carboxamide
-
6-(1-methyl-1H-pyrazol-5-yl)-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
6-(methylsulfonyl)-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
6-fluoro-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
6-[(1-methyl-1H-pyrazol-5-yl)amino]-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
methyl 3-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]propanoate
-
N,N'-(butane-1,4-diyl)bis[4-(adamantan-2-yl)piperazine-1-carboxamide]
-
N,N'-butane-1,4-diylbis[N'-[(3,5-dimethyladamantan-1-yl)methyl]urea]
-
N,N'-butane-1,4-diylbis[N'-[1-(adamantan-1-yl)-2-methylpropan-2-yl]urea]
-
N,N'-butane-1,4-diylbis[N'-[2-(adamantan-1-yl)-2-phenylethyl]urea]
-
N,N'-hexane-1,6-diylbis[N'-[(3,5-dimethyladamantan-1-yl)methyl]urea]
-
N,N'-hexane-1,6-diylbis[N'-[2-(adamantan-1-yl)-2-methylpropyl]urea]
-
N,N'-hexane-1,6-diylbis[N'-[2-(adamantan-1-yl)-2-phenylethyl]urea]
-
N,N'-octane-1,8-diylbis[N'-[(3,5-dimethyladamantan-1-yl)methyl]urea]
-
N,N'-octane-1,8-diylbis[N'-[2-(adamantan-1-yl)-2-methylpropyl]urea]
-
N,N'-octane-1,8-diylbis[N'-[2-(adamantan-1-yl)-2-phenylethyl]urea]
-
N,N'-[1,4-phenylenebis(methylene)]bis[N'-(3,5-dimethyladamantan-1-yl)urea]
-
N-(2,3-dihydro-1H-inden-1-yl)-4-oxo-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
N-(2,4-dichlorobenzyl)-1-(2-ethoxyethyl)-6-oxo-1,6-dihydropyridine-3-carboxamide
-
N-(2,4-dichlorobenzyl)-4-(4-fluorophenoxy)piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-(pyridin-2-ylmethyl)piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-(pyrimidin-2-yloxy)piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[(4-fluorophenyl)sulfonyl]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[2-(methylsulfonyl)phenoxy]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[3-(methylsulfonyl)phenoxy]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[4-(methylcarbamoyl)phenoxy]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[4-(methylsulfamoyl)phenoxy]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[4-(methylsulfonyl)phenoxy]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[4-(trifluoromethoxy)phenoxy]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-4-[[(4-fluorophenyl)sulfonyl]amino]piperidine-1-carboxamide
-
N-(2,4-dichlorobenzyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide
-
N-(2,4-dichlorobenzyl)-6-[2-(pyrrolidin-1-yl)ethyl]pyridine-3-carboxamide
-
N-(2-chloro-4-cyanobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-(2-chlorobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-(2-oxoadamantan-1-yl)-N'-1,3,5-triazatricyclo[3.3.1.13,7]decan-7-ylurea
-
N-(2-phenylcyclopropyl)-3',4'-dihydro-1H-spiro[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxamide
-
N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
-
N-(3,3-diphenylpropyl)-1-(2-ethoxyethyl)-6-oxo-1,6-dihydropyridine-3-carboxamide
-
N-(3,3-diphenylpropyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide
-
N-(3,3-diphenylpropyl)-6-[2-(pyrrolidin-1-yl)ethyl]pyridine-3-carboxamide
-
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'-(3,5,7-trimethyladamantan-1-yl)urea
-
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'-[(3-ethyladamantan-1-yl)methyl]urea
-
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-bromo-2-cyanobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-(4-chlorobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-(4-chlorophenyl)-3-(2-cyanoethyl)-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-(2-hydroxyethyl)-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-(3-hydroxypropyl)-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-phenyl-3-[2-(1H-tetrazol-5-yl)ethyl]piperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-[2-(dimethylamino)ethyl]-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-[2-oxo-2-(1H-tetrazol-5-ylamino)ethyl]-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-[3-(diethylamino)-3-oxopropyl]-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-[3-(methylamino)-3-oxopropyl]-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-[3-(morpholin-4-yl)-3-oxopropyl]-3-phenylpiperidine-1-carboxamide
-
N-(4-chlorophenyl)-3-[3-oxo-3-(1H-tetrazol-5-ylamino)propyl]-3-phenylpiperidine-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-[(1s,2R,3S)-2,3-diphenylcyclopropyl]-4-methylpiperazine-1-carboxamide
-
N-[(3'-chlorobiphenyl-4-yl)methyl]-3-methyl-3-phenylpiperidine-1-carboxamide
-
N-[(3,5-dimethyladamantan-1-yl)methyl]-N'-(3,5,7-trimethyladamantan-1-yl)urea
-
N-[(3-ethyladamantan-1-yl)methyl]-N'-(1-propanoylpiperidin-4-yl)urea
-
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-(adamantan-1-yl)ethyl]-N'-(3,5,7-trimethyladamantan-1-yl)urea
-
N-[1-(adamantan-1-yl)ethyl]-N'-[(3-ethyladamantan-1-yl)methyl]urea
-
N-[2-(adamantan-1-yl)butyl]-N'-(3,5,7-trimethyladamantan-1-yl)urea
-
N-[2-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-[2-(trifluoromethoxy)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-[2-chloro-4-(1H-tetrazol-5-yl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-[2-chloro-4-(methylsulfamoyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-[2-chloro-4-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-[3,3-bis-(4-fluorophenyl)-propyl]-2-(2,2,2-trifluoro-ethoxy)-isonicotinamide
-
N-[3,3-bis-(4-fluorophenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
-
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-4-methanesulfonyl-benzamide
-
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
-
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-nicotinamide
-
N-[3-[2-(4-chlorophenyl)ethyl]benzyl]-3-methyl-3-phenylpiperidine-1-carboxamide
-
N-[4-(1H-indol-5-yl)benzyl]-3-methyl-3-phenylpiperidine-1-carboxamide
-
N-[4-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-[4-chloro-2-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N-[5-[2-(2-ethoxyethoxy)ethoxy]pentyl]-N'-(4-hydroxyadamantan-1-yl)urea
-
N-[5-[2-(2-ethoxyethoxy)ethoxy]pentyl]-N'-(4-oxoadamantan-1-yl)urea
-
N-[[4'-(methylsulfonyl)biphenyl-4-yl]methyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
-
N1-(2,4-dichlorobenzyl)-N4-(2-methoxyethyl)piperidine-1,4-dicarboxamide
-
N1-(2,4-dichlorobenzyl)-N4-(tetrahydro-2H-pyran-4-yl)piperidine-1,4-dicarboxamide
-
N1-(2,4-dichlorobenzyl)-N4-[2-(methylsulfonyl)ethyl]piperidine-1,4-dicarboxamide
-
N1-(2,4-dichlorobenzyl)-N4-[2-(pyrrolidin-1-yl)ethyl]piperidine-1,4-dicarboxamide
-
N1-(2,4-dichlorobenzyl)-N4-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidine-1,4-dicarboxamide
-
[2-[(5-[[(adamantan-1-yl)carbamoyl]amino]pentyl)oxy]ethoxy]acetic acid
-
[6-(methylsulfonyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl][4-(trifluoromethyl)phenyl]methanone
-
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-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-[1-(2-methylbutanoyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea
-
-
1-[1-(2-methylbutanoyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-(2-methylpropanoyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea
-
-
1-[1-(2-methylpropanoyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-(3-methylbutanoyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-(cyclopropylcarbonyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-(cyclopropylsulfonyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-(propan-2-ylsulfonyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-[(2,2,2-trifluoroethyl)sulfonyl]piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea
-
-
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
-
-
1-[2-methyl-6-(methylamino)pyridin-4-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[2-methyl-6-(methylamino)pyrimidin-4-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[3-methyl-5-(methylamino)phenyl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4,6-bis(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-3-[1-(2-methylbutanoyl)piperidin-4-yl]urea
-
-
1-[4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-3-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]urea
-
-
1-[4-(dimethylamino)-6-methyl-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-(methylamino)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-(methylamino)-6-phenyl-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-(trifluoromethyl)phenyl]-3-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]urea
-
-
1-[4-cyclohexyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-ethyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethoxy)benzyl]piperidine-4-carboxamide
-
-
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[3-(trifluoromethoxy)benzyl]piperidine-4-carboxamide
-
-
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[[[4-bromo-2-(trifluoromethoxy)]-phenyl]methyl]-4-piperidinecarboxamide
-
-
1-[4-methyl-6-(methylamino)pyridin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-methyl-6-(methylamino)pyrimidin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-methyl-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-methyl-6-(propan-2-ylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-[(2-methoxyethyl)amino]-6-methyl-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[4-[[2-(dimethylamino)ethyl](methyl)amino]-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[6-methyl-2-(methylamino)pyrimidin-4-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
1-[6-methyl-4-(methylamino)pyridin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
-
-
12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester
-
selective soluble epoxide hydrolase inhibitor
2-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-N-[4-(trifluoromethoxy)phenyl]acetamide
-
-
benzo(a)pyrene
-
intratracheal instillation of benzo(a)pyrene significantly suppresses NF-kappaB translocation, sEH, thioredoxin reductase and catalase activities in lung tissue. Glycyrrhizic acid oral administration at 50 and 100 mg/kg body weight significantly shows protection of lung epithelium by suppression of caspases activities in lung tissue and reduction of total protein, total cells, elastase activity. Results indicate a strong correlation between amelioration of sEH and thioredoxin reductase activities, and NF-kappaB activation
methyl 3-chloro-4-[([[6-(3,3,3-trifluoropropoxy)pyridin-3-yl]carbonyl]amino)methyl]benzenesulfinate
-
-
methyl 4-[([[1-butyl-2-(3,4,5-trimethoxyphenyl)-1H-benzimidazol-5-yl]carbonyl]amino)methyl]-3-methoxybenzenesulfinate
-
-
N,N'-dicyclohexylurea
-
specific inhibitor, decreases the enzyme activity and blood pressure in spontaneously hypertensive rats, IC50 with different substrates, overview
N-(2,4-dichlorobenzyl)-1-[(2,4,6-trimethylphenyl)sulfonyl]piperidine-4-carboxamide
-
-
N-(2-cyanobenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
-
-
N-(2-methoxybenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
-
-
N-(2-methylbenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
-
-
N-benzyl-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
-
-
N-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-2-[4-(trifluoromethoxy)phenyl]acetamide
-
-
N-[4-fluoro-2-(trifluoromethyl)benzyl]-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
-
-
trans-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid
-
potent sEH inhibitor
trans-4-[4-[3-(4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy]benzoic acid
-
-
trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid
t-AUCB, a tight binding inhibitor of enzyme sEH
12-(3-adamantan-1-yl-ureido)-dodecanoic acid
-
orally active inhibitor. Inhibition of soluble epoxide hydrolase is effective in persistently reducing blood pressure in female spontaneously hypertensive rats when 12-(3-adamantan-1-yl-ureido)-dodecanoic acid is applied during the perinatal phase
12-(3-adamantan-1-yl-ureido)dodecanoic acid
-
selective soluble epoxide hydrolase inhibitor
AUDA
-
i.e. 12-(3-adamantan-1-yl-ureido) dodecanoic acid, inhibition in vivo by intracerebroventricular delivery
additional information
design and synthesis of a series of potent nicotinamide inhibitors of soluble epoxides hydrolase, structure-guided optimization, overview
-
additional information
evaluation of spirocyclic secondary amine-derived trisubstituted ureas as highly potent, bioavailable and selective soluble epoxide hydrolase inhibitors, overview
-
additional information
inhibitor screening, design, and synthesis, overview. Inhibition of sEH leads to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects
-
additional information
SEH inhibition antagonizes neointimal formation in vivo in an endothelium-dependent manner
-
additional information
synthesis and structure-based optimization of arylamides sEH inhibitors based on the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide, overview. Assessment of inhibitor stability in liver microsomes, overview
-
additional information
treatment with sEH inhibitors reduces blood pressure in several animal models of hypertension
-
additional information
design and synthesis of three substituted cyclopropyl urea derivatives as strong sEH inhibitors using X-ray co-crystal structure of sEH catalytic domain and 3-[4-[(1-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid, overview. cis-Configuration together with a phenyl group result in increased human and rat sEH inhibitory activity with minimal species difference
-
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
-
no inhibition by Mn2+, Ba2+, Mg2+, and Ca2+ 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
-
pulmonary sEH protein expression and activity are impaired in monocrotaline-treated rats
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
the enzyme is induced by clofibrate in liver not in epididymis
-
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
-
additional information
-
sEH is specifically up-regulated by angiotensin II
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0147
(10R)-hydroxy-(11S,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoic acid
-
pH 7.4, 37°C
0.0046
(8R)-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoic acid
-
pH 7.4, 37°C
0.008
trans-stilbene oxide
-
recombinant fusion protein expressed in E. coli
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
0.6
(10R)-hydroxy-(11S,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoic acid
-
pH 7.4, 37°C
1.88
(8R)-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoic acid
-
pH 7.4, 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
51
(10R)-hydroxy-(11S,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoic acid
-
pH 7.4, 37°C
450
(8R)-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoic acid
-
pH 7.4, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000011
4-(1H-pyrrol-1-yl)-N-[4-(trifluoromethoxy)phenyl]-piperidinecarboxamide
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000002
(3R)-N-[(1s,2R,3S)-2,3-diphenylcyclopropyl]-3-[(4-fluorobenzene-1-sulfonyl)amino]piperidine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.0000008
(3R)-N-[(1s,2R,3S)-2,3-diphenylcyclopropyl]-3-[(methanesulfonyl)amino]piperidine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.000024
(R)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
Rattus norvegicus
-
0.000087
(R)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
Rattus norvegicus
-
0.000006
(S)-4-cyano-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-benzamide
Rattus norvegicus
-
0.000007
(S)-N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-hydroxy-nicotinamide
Rattus norvegicus
-
0.00001
1-(3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl)-3-phenylpropan-1-one
Rattus norvegicus
-
0.001
1-[(2,4-dichlorobenzyl)carbamoyl]piperidine-4-carboxylic acid
Rattus norvegicus
-
0.003
1-[[4-(trifluoromethoxy)phenyl]carbamoyl]piperidine-4-carboxylic acid
Rattus norvegicus
-
0.000004
2-(2,4-dichlorophenyl)-1-[6-(methylsulfonyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl]ethanone
Rattus norvegicus
-
0.00011
2-(hydroxymethyl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000029
2-methyl-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.00001
3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl[4-(trifluoromethyl)phenyl]methanone
Rattus norvegicus
-
0.000026
3-(3-amino-3-oxopropyl)-N-(4-chlorophenyl)-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000007
3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propylamine
Rattus norvegicus
-
0.0015
3-(hydroxymethyl)-N-(2-methylbenzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.003
3-(hydroxymethyl)-N-(3-methylbenzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.0029
3-(hydroxymethyl)-N-(4-methylbenzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.000019
3-(hydroxymethyl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000003
3-methyl-3-phenyl-N-(4-(pyridin-3-yl)benzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.000249
3-methyl-3-phenyl-N-(pyridin-4-yl)piperidine-1-carboxamide
Rattus norvegicus
-
0.000006
3-methyl-3-phenyl-N-[3-(pyridin-3-yl)propyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000004
3-methyl-3-phenyl-N-[3-[(1S,2S)-2-phenylcyclopropyl]benzyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000019
3-methyl-3-phenyl-N-[3-[2-(quinoxalin-6-yl)ethyl]benzyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000011
3-methyl-3-phenyl-N-[[2'-(trifluoromethyl)biphenyl-4-yl]methyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000012
3-methyl-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.00029
3-[1-[(4-chlorophenyl)carbamoyl]-3-(pyridin-2-yl)piperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.000331
3-[1-[(4-chlorophenyl)carbamoyl]-3-(pyridin-3-yl)piperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.000467
3-[1-[(4-chlorophenyl)carbamoyl]-3-(pyridin-4-yl)piperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.000176
3-[1-[(4-chlorophenyl)carbamoyl]-3-[3-(trifluoromethyl)phenyl]piperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.00012
3-[1-[(4-chlorophenyl)carbamoyl]-3-[4-(trifluoromethyl)phenyl]piperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.000413
3-[3-(biphenyl-4-yl)-1-[(4-chlorophenyl)carbamoyl]piperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.0001
3-[4-[(1-[[(1R,3S)-2,2-dimethyl-3-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
Rattus norvegicus
pH and temperature not specified in the publication
0.0000556
3-[4-[(1-[[(1S,2R)-2-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
Rattus norvegicus
pH and temperature not specified in the publication
0.0000117
3-[4-[(1-[[(1S,2R,3R)-2-methyl-3-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
Rattus norvegicus
pH and temperature not specified in the publication
0.0000032
3-[4-[(1-[[(1s,2R,3S)-2,3-bis(4-fluorophenyl)cyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
Rattus norvegicus
pH and temperature not specified in the publication
0.0000039
3-[4-[(1-[[(1s,2R,3S)-2,3-diphenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
Rattus norvegicus
pH and temperature not specified in the publication
0.0001
3-[4-[(1-[[(1S,2S,3R)-2-methyl-3-phenylcyclopropyl]carbamoyl]piperidin-4-yl)oxy]phenyl]propanoic acid
Rattus norvegicus
pH and temperature not specified in the publication
0.000031
4'-hydroxy-N-(2-phenylcyclopropyl)-3',4'-dihydro-1H-spiro[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxamide
Rattus norvegicus
-
0.000011
4-(1H-pyrrol-1-yl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000039
4-(2-cyanophenoxy)-N-(2,4-dichlorobenzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.0000049
4-(3-cyanophenoxy)-N-(2,4-dichlorobenzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.0000059
4-(4-chlorophenoxy)-N-(2,4-dichlorobenzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.0000042
4-(4-cyanophenoxy)-N-(2,4-dichlorobenzyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.000046
4-(hydroxymethyl)-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000053
4-([1-[(2,4-dichlorobenzyl)carbamoyl]piperidin-4-yl]oxy)benzoic acid
Rattus norvegicus
-
0.000015
4-benzyl-N-(2,4-dichlorobenzyl)-4-hydroxypiperidine-1-carboxamide
Rattus norvegicus
-
0.000018
4-methyl-N-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000039
4-oxo-N-(1,2,3,4-tetrahydronaphthalen-2-yl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000007
4-oxo-N-(2-phenylcyclopropyl)-6-(pyridin-4-yl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000021
4-oxo-N-(3-phenylcyclopentyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000028
4-oxo-N-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000009
4-oxo-N-[(1S,2R)-2-phenylcyclopropyl]-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000176
4-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]butanoic acid
Rattus norvegicus
-
0.0000281
4-[[(1r,4r)-4-[[(3,5,7-trimethyladamantan-1-yl)carbamoyl]amino]cyclohexyl]oxy]benzoic acid
Rattus norvegicus
pH 7.4, 37°C
0.00012
5-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]pentanoic acid
Rattus norvegicus
-
0.00002 - 0.000049
6'-(methylsulfonyl)-N-(2-phenylcyclopropyl)-1H,4'H-spiro[azepane-4,3'-chromene]-1-carboxamide
0.000021
6-(1-methyl-1H-pyrazol-5-yl)-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000012 - 0.000029
6-(methylsulfonyl)-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
0.000018
6-fluoro-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000013
6-[(1-methyl-1H-pyrazol-5-yl)amino]-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000003
methyl 3-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]propanoate
Rattus norvegicus
-
0.000307
N-(1,2-benzoxazol-3-yl)-3-methyl-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000035
N-(2,3-dihydro-1H-inden-1-yl)-4-oxo-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000006
N-(2,4-dichlorobenzyl)-1-(2-ethoxyethyl)-6-oxo-1,6-dihydropyridine-3-carboxamide
Rattus norvegicus
-
0.000041
N-(2,4-dichlorobenzyl)-3-(hydroxymethyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.000003
N-(2,4-dichlorobenzyl)-3-methyl-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.0000061
N-(2,4-dichlorobenzyl)-4-(4-fluorophenoxy)piperidine-1-carboxamide
Rattus norvegicus
-
0.000006
N-(2,4-dichlorobenzyl)-4-(pyridin-2-yl)piperazine-1-carboxamide
Rattus norvegicus
-
0.000012
N-(2,4-dichlorobenzyl)-4-(pyridin-2-ylmethyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.000015
N-(2,4-dichlorobenzyl)-4-(pyrimidin-2-yloxy)piperidine-1-carboxamide
Rattus norvegicus
-
0.000027
N-(2,4-dichlorobenzyl)-4-hydroxy-4-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.0000043
N-(2,4-dichlorobenzyl)-4-phenoxypiperidine-1-carboxamide
Rattus norvegicus
-
0.000039
N-(2,4-dichlorobenzyl)-4-[(4-fluorophenyl)sulfonyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000049
N-(2,4-dichlorobenzyl)-4-[2-(methylsulfonyl)phenoxy]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000046
N-(2,4-dichlorobenzyl)-4-[3-(methylsulfonyl)phenoxy]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000042
N-(2,4-dichlorobenzyl)-4-[4-(methylcarbamoyl)phenoxy]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000052
N-(2,4-dichlorobenzyl)-4-[4-(methylsulfamoyl)phenoxy]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000056
N-(2,4-dichlorobenzyl)-4-[4-(methylsulfonyl)phenoxy]piperidine-1-carboxamide
Rattus norvegicus
-
0.000012
N-(2,4-dichlorobenzyl)-4-[4-(trifluoromethoxy)phenoxy]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000056
N-(2,4-dichlorobenzyl)-4-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000017
N-(2,4-dichlorobenzyl)-4-[[(4-fluorophenyl)sulfonyl]amino]piperidine-1-carboxamide
Rattus norvegicus
-
0.0000073
N-(2,4-dichlorobenzyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.00033
N-(2,4-dichlorobenzyl)-6-oxo-1,6-dihydropyridine-3-carboxamide
Rattus norvegicus
-
0.0005
N-(2,4-dichlorobenzyl)-6-[2-(pyrrolidin-1-yl)ethyl]pyridine-3-carboxamide
Rattus norvegicus
-
0.000008
N-(2-chloro-4-cyanobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000022
N-(2-chlorobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000021
N-(2-phenylcyclopropyl)-3',4'-dihydro-1H-spiro[piperidine-4,2'-pyrano[3,2-b]pyridine]-1-carboxamide
Rattus norvegicus
-
0.000011
N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000004
N-(3,3-diphenylpropyl)-1-(2-ethoxyethyl)-6-oxo-1,6-dihydropyridine-3-carboxamide
Rattus norvegicus
-
0.0000078
N-(3,3-diphenylpropyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.00001
N-(3,3-diphenylpropyl)-6-oxo-1,6-dihydropyridine-3-carboxamide
Rattus norvegicus
-
0.000009
N-(3,3-diphenylpropyl)-6-[2-(pyrrolidin-1-yl)ethyl]pyridine-3-carboxamide
Rattus norvegicus
-
0.0002
N-(3,4-dichlorobenzyl)-3-(hydroxymethyl)piperidine-1-carboxamide
Rattus norvegicus
-
0.0000249
N-(3,5,7-trimethyladamantan-1-yl)-4-([[(3,5,7-trimethyladamantan-1-yl)carbamoyl]amino]methyl)piperidine-1-carboxamide
Rattus norvegicus
pH 7.4, 37°C
0.0000018
N-(3,5-dimethyladamantan-1-yl)-N'-(1-propanoylpiperidin-4-yl)urea
Rattus norvegicus
pH 7.4, 37°C
0.0000971
N-(3,5-dimethyladamantan-1-yl)-N'-(3,5,7-trimethyladamantan-1-yl)urea
Rattus norvegicus
pH 7.4, 37°C
0.000007
N-(4-bromo-2-cyanobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000007
N-(4-chlorobenzyl)-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000016
N-(4-chlorophenyl)-3-(2-cyanoethyl)-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000015
N-(4-chlorophenyl)-3-(2-hydroxyethyl)-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.00001
N-(4-chlorophenyl)-3-(3-hydroxypropyl)-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000005
N-(4-chlorophenyl)-3-methyl-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000059
N-(4-chlorophenyl)-3-phenyl-3-[2-(1H-tetrazol-5-yl)ethyl]piperidine-1-carboxamide
Rattus norvegicus
-
0.000119
N-(4-chlorophenyl)-3-[2-(dimethylamino)ethyl]-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000034
N-(4-chlorophenyl)-3-[2-oxo-2-(1H-tetrazol-5-ylamino)ethyl]-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000031
N-(4-chlorophenyl)-3-[3-(diethylamino)-3-oxopropyl]-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000032
N-(4-chlorophenyl)-3-[3-(methylamino)-3-oxopropyl]-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.0001
N-(4-chlorophenyl)-3-[3-(morpholin-4-yl)-3-oxopropyl]-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000026
N-(4-chlorophenyl)-3-[3-oxo-3-(1H-tetrazol-5-ylamino)propyl]-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000006
N-(biphenyl-3-yl)-3-methyl-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.0000051
N-adamantan-1-yl-N'-(3,5,7-trimethyladamantan-1-yl)urea
Rattus norvegicus
pH 7.4, 37°C
0.0000277
N-[(1s,2R,3S)-2,3-diphenylcyclopropyl]-4-methylpiperazine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.0000002
N-[(1s,2R,3S)-2,3-diphenylcyclopropyl]piperidine-1-carboxamide
Rattus norvegicus
pH and temperature not specified in the publication
0.000007
N-[(3'-chlorobiphenyl-4-yl)methyl]-3-methyl-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.00016
N-[2-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000006
N-[2-(trifluoromethoxy)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.00018
N-[2-chloro-4-(1H-tetrazol-5-yl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000019
N-[2-chloro-4-(methylsulfamoyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000016
N-[2-chloro-4-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.000006
N-[3,3-bis-(4-fluorophenyl)-propyl]-2-(2,2,2-trifluoro-ethoxy)-isonicotinamide
Rattus norvegicus
-
0.000007
N-[3,3-bis-(4-fluorophenyl)-propyl]-4-methanesulfonyl-benzamide
Rattus norvegicus
-
0.000009
N-[3,3-bis-(4-fluorophenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
Rattus norvegicus
-
0.000007
N-[3,3-bis-(4-fluorophenyl)-propyl]-6-hydroxy-nicotinamide
Rattus norvegicus
-
0.000008
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-4-methanesulfonyl-benzamide
Rattus norvegicus
-
0.000006
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-6-(2,2,2-trifluoro-ethoxy)-nicotinamide
Rattus norvegicus
-
0.000014
N-[3-(4-fluorophenyl)-3-(4-methanesulfonyl-phenyl)-propyl]-nicotinamide
Rattus norvegicus
-
0.000005
N-[3-[2-(4-chlorophenyl)ethyl]benzyl]-3-methyl-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000006
N-[4-(1H-indol-5-yl)benzyl]-3-methyl-3-phenylpiperidine-1-carboxamide
Rattus norvegicus
-
0.000025
N-[4-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.003
N-[4-(trifluoromethoxy)phenyl]-1,4'-bipiperidine-1'-carboxamide
Rattus norvegicus
-
0.000011
N-[4-chloro-2-(methylsulfonyl)benzyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.0000043
N-[[4'-(methylsulfonyl)biphenyl-4-yl]methyl]-6-(3,3,3-trifluoropropoxy)pyridine-3-carboxamide
Rattus norvegicus
-
0.00021
N1-(2,4-dichlorobenzyl)-N4-(2-methoxyethyl)piperidine-1,4-dicarboxamide
Rattus norvegicus
-
0.00018
N1-(2,4-dichlorobenzyl)-N4-(tetrahydro-2H-pyran-4-yl)piperidine-1,4-dicarboxamide
Rattus norvegicus
-
0.00023
N1-(2,4-dichlorobenzyl)-N4-[2-(methylsulfonyl)ethyl]piperidine-1,4-dicarboxamide
Rattus norvegicus
-
0.00022
N1-(2,4-dichlorobenzyl)-N4-[2-(pyrrolidin-1-yl)ethyl]piperidine-1,4-dicarboxamide
Rattus norvegicus
-
0.00015
N1-(2,4-dichlorobenzyl)-N4-[2-(tetrahydro-2H-pyran-4-yl)ethyl]piperidine-1,4-dicarboxamide
Rattus norvegicus
-
0.000398
[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]acetic acid
Rattus norvegicus
-
0.000019
[6-(methylsulfonyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidin]-1'-yl][4-(trifluoromethyl)phenyl]methanone
Rattus norvegicus
-
0.000005
1-adamantan-1-yl-3-(5-[2-(2-ethoxyethoxy)ethoxy]pentyl)urea
Rattus norvegicus
-
pH 7.5, 30°C
0.000079
1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl)urea
Rattus norvegicus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.0000291
1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)-urea
Rattus norvegicus
-
in sodium phosphate buffer (0.1 M, pH 7.4), at 30°C
0.0000133
1-[1-(2-methylpropanoyl)piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea
Rattus norvegicus
-
in sodium phosphate buffer (0.1 M, pH 7.4), at 30°C
0.0000018
1-[1-(2-methylpropanoyl)piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
Rattus norvegicus
-
in sodium phosphate buffer (0.1 M, pH 7.4), at 30°C
0.00002
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethoxy)phenyl]urea
Rattus norvegicus
-
in sodium phosphate buffer (0.1 M, pH 7.4), at 30°C
0.00000125
1-[1-[(2S)-2-methylbutanoyl]piperidin-4-yl]-3-[4-(trifluoromethyl)phenyl]urea
Rattus norvegicus
-
IC50 below 0.00000125 mM, in sodium phosphate buffer (0.1 M, pH 7.4), at 30°C
0.000126
1-[2-methyl-6-(methylamino)pyridin-4-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000005
1-[2-methyl-6-(methylamino)pyrimidin-4-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000032
1-[3-methyl-5-(methylamino)phenyl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00002
1-[4,6-bis(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
1-[4-(dimethylamino)-6-methyl-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00004
1-[4-(methylamino)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
1-[4-(methylamino)-6-phenyl-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
1-[4-cyclohexyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000004
1-[4-ethyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethoxy)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000003
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.0004 - 0.00063
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[3-(trifluoromethoxy)benzyl]piperidine-4-carboxamide
0.00001
1-[4-methyl-6-(methylamino)pyridin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00016
1-[4-methyl-6-(methylamino)pyrimidin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
1-[4-methyl-6-(morpholin-4-yl)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
1-[4-methyl-6-(propan-2-ylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
1-[4-[(2-methoxyethyl)amino]-6-methyl-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00008
1-[4-[[2-(dimethylamino)ethyl](methyl)amino]-6-(methylamino)-1,3,5-triazin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00004
1-[6-methyl-2-(methylamino)pyrimidin-4-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.001585
1-[6-methyl-4-(methylamino)pyridin-2-yl]-N-[2-(trifluoromethyl)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000011
12-(3-adamantan-1-ylureido)dodecanoic acid
Rattus norvegicus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.000005
12-(3-adamantan-1-ylureido)dodecanoic acid butyl ester
Rattus norvegicus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.000007
cis-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid
Rattus norvegicus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.000006
N-(1-acetylpiperidin-4-yl)-N'-(adamant-1-yl)urea
Rattus norvegicus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.00008
N-(2-cyanobenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001 - 0.0016
N-(2-methoxybenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
0.0002
N-(2-methylbenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.0002
N-benzyl-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000003
N-[4-fluoro-2-(trifluoromethyl)benzyl]-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000008
trans-4-[4-(3-adamantan-1-yl-ureido)cyclohexyloxy]benzoic acid
Rattus norvegicus
-
in bis-Tris/HCl buffer, pH 7.0, at 25°C
0.000008
trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid
Rattus norvegicus
-
pH 7.5, 30°C
0.00007
3-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.000076
3-[1-[(4-chlorophenyl)carbamoyl]-3-phenylpiperidin-3-yl]propanoic acid
Rattus norvegicus
-
0.00002
6'-(methylsulfonyl)-N-(2-phenylcyclopropyl)-1H,4'H-spiro[azepane-4,3'-chromene]-1-carboxamide
Rattus norvegicus
-
0.000049
6'-(methylsulfonyl)-N-(2-phenylcyclopropyl)-1H,4'H-spiro[azepane-4,3'-chromene]-1-carboxamide
Rattus norvegicus
-
0.000012
6-(methylsulfonyl)-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000023
6-(methylsulfonyl)-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.000029
6-(methylsulfonyl)-4-oxo-N-(2-phenylcyclopropyl)-3,4-dihydro-1'H-spiro[chromene-2,4'-piperidine]-1'-carboxamide
Rattus norvegicus
-
0.0004
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[3-(trifluoromethoxy)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.00063
1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]-N-[3-(trifluoromethoxy)benzyl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000001
N-(2-methoxybenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
0.0016
N-(2-methoxybenzyl)-1-[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]piperidine-4-carboxamide
Rattus norvegicus
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
-
pH 6.0: about 35% of maximal activity, pH 9.0: about 60% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
aortic intima of both spontaneously hypertensive rats and rats infused with angiotensin II exhibits an elevated level of soluble epoxide hydrolase
additional information
laboratory rats have by far the lowest levels of hepatic sEH among the mammals studied
-
expression of soluble epoxide hydrolase is significantly lower in stroke-prone than in stroke-resitant rats. Identification of 3 polymorphisms that significantly influence promoter transcriptional activity in vitro
-
the activity for epoxyeicosatrienoic acids is elevated 5 to 54fold in renal cortical S9 fraction from the spontaneously hypertensive rats compared to normotensive Wistar-Kyoto rats
-
-
additional information
-
enzyme expression is reduced in spontaneously hypertensive rats compared to normotensive rats
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
-
-
recombinant wild-type enzyme and some recombinant modified enzymes in V79 cells
-
the enzyme contains an impaired peroxisomal targeting sequence leading to dual localization
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
physiological function
additional information
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
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
the enzyme and vascular remodeling are associated with cardiovascular disease. Inhibition of SEH prevents smooth muscle cell proliferation in vitro and affects vascular remodeling in vivo, but induces cell proliferation in the left carotid of spontaneously hypertensive stroke-prone rats
physiological function
soluble epoxide hydrolase is a key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids, EETs
physiological function
mammalian soluble epoxide hydrolase (sEH) is involved in mediating the metabolism of the endogenous lipid 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
additional information
inhibition of sEH leads to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects
additional information
treatment with sEH inhibitors reduces blood pressure in several animal models of hypertension
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_RAT
554
0
62340
Swiss-Prot
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
65000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
additional information
-
structure analysis, amino acid sequence analysis and comparisons, the enzyme forms an alpha/beta hydrolase fold
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 30% (w/v) PEG 3350, 0-10% (w/v) sucrose, at 4°C
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C780T
naturally occuring mutation involved in renal cortex of Wistar-Kyoto rats
G1465A
naturally occuring mutation involved in renal cortex of Wistar-Kyoto rats
G405A
naturally occuring mutation involved in renal cortex of Wistar-Kyoto rats
G560A
naturally occuring mutation involved in renal cortex of Wistar-Kyoto rats
E404D
-
site-directed mutagenesis, the mutant enzyme shows unaltered enantioselectivity with stearic acid oxide substrate compared to the wild-type enzyme
H332Q
-
strong decrease in enzymatic activity due to a change in substrate affinity, Km deviates only slightly from that of the wild-type enzyme, Vmax is reduced to 5% of the wild-type enzyme
W540L
additional information
W540L
-
strong decrease in enzymatic activity due to a change in substrate affinity, Km deviates only slightly from that of the wild-type enzyme
additional information
Ephx2 deletion antagonizes neointimal formation in vivo in an endothelium-dependent manner
additional information
increased sEH gene expression and activity along with renal eicosanoid metabolism participate in the pathogenesis of hypertension in SHRs
additional information
-
construction of mutants with point mutations in a wild-type SKI sequence motif, some mutant enzymes show altered subcellular localization, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme from liver to homogeneity by ultracentrifugation and affinity chromatography on a benzyl thio resin using 4-fluorochalcone oxide as eluent
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the enzyme from full-length gene in Escherichia coli strain BL21-AI
-
stable expression of GFP-tagged wild-type and modified enzymes in V79 Chinese hamster cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
sEH is a target for drug design, since inhibition of sEH leads to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties
medicine
sEH is a potential therapeutic target in the treatment of ischemic stroke
pharmacology
SEH inhibition might have a potential for flow-induced vascular remodeling and neointimal formation
medicine
medicine
-
the enzyme is a therapeutic target for control of blood pressure
medicine
-
expression of soluble epoxide hydrolase is significantly lower in stroke-prone than in stroke-resitant rats. Identification of 3 polymorphisms that significantly influence promoter transcriptional activity in vitro
medicine
-
ovariectomized female rats with and without estradiol replacement undergoing 2-h middle cerebral artery occlusion. Estradiol reduces basal and post-ischemic soluble epoxide hydrolase expression. Middle cerebral artery occlusion strongly induces mRNA levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 1beta, which is attenuated in enzyme knock-outs, but not by enzyme inhibitors
medicine
-
soluble epoxide hydrolase is a susceptibility factor for heart failure
medicine
-
soluble epoxide hydrolase plays an essential role in angiotensin II-induced cardiac hypertrophy
medicine
-
inhibition of soluble epoxide hydrolase by orally active inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid is effective in persistently reducing blood pressure in female spontaneously hypertensive rats when 12-(3-adamantan-1-yl-ureido)-dodecanoic acid is applied during the perinatal phase. This is accompanied by marked increases in major renal arachidonic acid epoxides and decreases in renal lipoxygenase products of arachidonic acid. Early inhibition of SEH induces a delayed increase in renal 5-HETE at 24 weeks, in contrast to a decrease at 2 weeks. Inhibition of SEH in female spontaneously hypertensive rats from 8 to 12 weeks does not reduce blood but causes profound decreases in renal 15(S)-HETrE, LTB4, TBX2, 5-HETE, and 20-HETE and increases in TriHOMEs. In male spontaneously hypertensive rats, blood pressure reduction after perinatal AUDA is transient
medicine
-
intratracheal instillation of benzo(a)pyrene significantly suppresses NF-kappaB translocation, sEH, thioredoxin reductase and catalase activities in lung tissue. Glycyrrhizic acid oral administration at 50 and 100 mg/kg body weight significantly shows protection of lung epithelium by suppression of caspases activities in lung tissue and reduction of total protein, total cells, elastase activity. Results indicate a strong correlation between amelioration of sEH and thioredoxin reductase activities, and NF-kappaB activation
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
Wang, P.; Meijer, J.; Guengerich, F.P.
Purification of human liver cytosolic epoxide hydrolase and comparison to the microsomal enzyme
Biochemistry
21
5769-5776
1982
Homo sapiens, Rattus norvegicus
Meijer, J.; DePierre, J.W.
Cytosolic epoxide hydrolase
Chem. Biol. Interact.
64
207-249
1988
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus
Schladt, L.; Hartman, R.; Woerner, W.; Thomas, H.; Oesch, F.
Purification and characterization of rat-liver cytosolic epoxide hydrolase
Eur. J. Biochem.
176
31-37
1988
Rattus norvegicus
Arand, M.; Wagner, H.; Oesch, F.
Asp333, Asp495, and His523 form the catalytic triad of rat soluble epoxide hydrolase
J. Biol. Chem.
271
4223-4229
1996
Rattus norvegicus
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
Thomas, H.; Schladt, L.; Doehmer, J.; Knehr, M.; Oesch, F.
Rat and human liver cytosolic epoxide hydrolases: evidence for multiple forms at the level of protein and mRNA
Environ. Health Perspect.
88
49-55
1990
Homo sapiens, Rattus norvegicus
Summerer, S.; Hanano, A.; Utsumi, S.; Arand, M.; Schuber, F.; Blee, E.
Stereochemical features of the hydrolysis of 9,10-epoxystearic acid catalysed by plant and mammalian epoxide hydrolases
Biochem. J.
366
471-480
2002
Rattus norvegicus
DuTeaux, S.B.; Newman, J.W.; Morisseau, C.; Fairbairn, E.A.; Jelks, K.; Hammock, B.D.; Miller, M.G.
Epoxide hydrolases in the rat epididymis: possible roles in xenobiotic and endogenous fatty acid metabolism
Toxicol. Sci.
78
187-195
2004
Rattus norvegicus
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
Lacourciere, G.M.; Armstrong, R.N.
Microsomal ans soluble epoxide hydrolases are members of the same family of C-X bond hydrolase enzymes
Chem. Res. Toxicol.
7
121-124
1994
Rattus norvegicus
Yu, Z.; Xu, F.; Huse, L.M.; Morisseau, C.; Draper, A.J.; Newman, J.W.; Parker, C.; Graham, L.; Engler, M.M.; Hammock, B.D.; Zeldin, D.C.; Kroetz, D.L.
Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids
Circ. Res.
87
992-998
2000
Rattus norvegicus
Sellers, K.W.; Sun, C.; Diez-Freire, C.; Waki, H.; Morisseau, C.; Falck, J.R.; Hammock, B.D.; Paton, J.F.; Raizada, M.K.
Novel mechanism of brain soluble epoxide hydrolase-mediated blood pressure regulation in the spontaneously hypertensive rat
FASEB J.
19
626-628
2005
Rattus norvegicus
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
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)
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
Koerner, I.P.; Zhang, W.; Cheng, J.; Parker, S.; Hurn, P.D.; Alkayed, N.J.
Soluble epoxide hydrolase: regulation by estrogen and role in the inflammatory response to cerebral ischemia
Front. Biosci.
13
2833-2841
2008
Rattus norvegicus
Corenblum, M.J.; Wise, V.E.; Georgi, K.; Hammock, B.D.; Doris, P.A.; Fornage, M.
Altered soluble epoxide hydrolase gene expression and function and vascular disease risk in the stroke-prone spontaneously hypertensive rat
Hypertension
51
567-573
2008
Rattus norvegicus
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
Ai, D.; Fu, Y.; Guo, D.; Tanaka, H.; Wang, N.; Tang, C.; Hammock, B.D.; Shyy, J.Y.; Zhu, Y.
Angiotensin II up-regulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo
Proc. Natl. Acad. Sci. USA
104
9018-9023
2007
Bos taurus, Homo sapiens, Rattus norvegicus
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
Olearczyk, J.J.; Quigley, J.E.; Mitchell, B.C.; Yamamoto, T.; Kim, I.H.; Newman, J.W.; Luria, A.; Hammock, B.D.; Imig, J.D.
Administration of a substituted adamantyl urea inhibitor of soluble epoxide hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats
Clin. Sci.
116
61-70
2009
Rattus norvegicus
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
Li, J.; Carroll, M.A.; Chander, P.N.; Falck, J.R.; Sangras, B.; Stier, C.T.
Soluble epoxide hydrolase inhibitor, AUDA, prevents early salt-sensitive hypertension
Front. Biosci.
13
3480-3487
2008
Rattus norvegicus
Revermann, M.; Barbosa-Sicard, E.; Dony, E.; Schermuly, R.T.; Morisseau, C.; Geisslinger, G.; Fleming, I.; Hammock, B.D.; Brandes, R.P.
Inhibition of the soluble epoxide hydrolase attenuates monocrotaline-induced pulmonary hypertension in rats
J. Hypertens.
27
322-331
2009
Rattus norvegicus
Rawal, S.; Morisseau, C.; Hammock, B.D.; Shivachar, A.C.
Differential subcellular distribution and colocalization of the microsomal and soluble epoxide hydrolases in cultured neonatal rat brain cortical astrocytes
J. Neurosci. Res.
87
218-227
2009
Rattus norvegicus
Monti, J.; Fischer, J.; Paskas, S.; Heinig, M.; Schulz, H.; Goesele, C.; Heuser, A.; Fischer, R.; Schmidt, C.; Schirdewan, A.; Gross, V.; Hummel, O.; Maatz, H.; Patone, G.; Saar, K.; Vingron, M.; Weldon, S.M.; Lindpaintner, K.; Hammock, B.D.; Rohde, K.; Dietz, R.; Cook, S.A.; Schunck, W.H.; Luft, F.C.; Hub, H.u.b.n.
Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease
Nat. Genet.
40
529-537
2008
Homo sapiens, Rattus norvegicus
Inceoglu, B.; Jinks, S.L.; Ulu, A.; Hegedus, C.M.; Georgi, K.; Schmelzer, K.R.; Wagner, K.; Jones, P.D.; Morisseau, C.; Hammock, B.D.
Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways
Proc. Natl. Acad. Sci. USA
105
18901-18906
2008
Rattus norvegicus
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
Simpkins, A.N.; Rudic, R.D.; Roy, S.; Tsai, H.J.; Hammock, B.D.; Imig, J.D.
Soluble epoxide hydrolase inhibition modulates vascular remodeling
Am. J. Physiol. Heart Circ. Physiol.
298
H795-H806
2010
Rattus norvegicus (P80299)
Shen, H.C.; Ding, F.X.; Wang, S.; Xu, S.; Chen, H.S.; Tong, X.; Tong, V.; Mitra, K.; Kumar, S.; Zhang, X.; Chen, Y.; Zhou, G.; Pai, L.Y.; Alonso-Galicia, M.; Chen, X.; Zhang, B.; Tata, J.R.; Berger, J.P.; Colletti, S.L.
Discovery of spirocyclic secondary amine-derived tertiary ureas as highly potent, selective and bioavailable soluble epoxide hydrolase inhibitors
Bioorg. Med. Chem. Lett.
19
3398-3404
2009
Homo sapiens (P34913), Rattus norvegicus (P80299)
Shen, H.C.; Ding, F.X.; Deng, Q.; Xu, S.; Chen, H.S.; Tong, X.; Tong, V.; Zhang, X.; Chen, Y.; Zhou, G.; Pai, L.Y.; Alonso-Galicia, M.; Zhang, B.; Roy, S.; Tata, J.R.; Berger, J.P.; Colletti, S.L.
Discovery of 3,3-disubstituted piperidine-derived trisubstituted ureas as highly potent soluble epoxide hydrolase inhibitors
Bioorg. Med. Chem. Lett.
19
5314-5320
2009
Homo sapiens (P34913), Homo sapiens, Rattus norvegicus (P80299)
Taylor, S.J.; Soleymanzadeh, F.; Eldrup, A.B.; Farrow, N.A.; Muegge, I.; Kukulka, A.; Kabcenell, A.K.; De Lombaert, S.
Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase
Bioorg. Med. Chem. Lett.
19
5864-5868
2009
Homo sapiens (P34913), Homo sapiens, Rattus norvegicus (P80299)
Eldrup, A.B.; Soleymanzadeh, F.; Farrow, N.A.; Kukulka, A.; De Lombaert, S.
Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase
Bioorg. Med. Chem. Lett.
20
571-575
2010
Rattus norvegicus (P80299)
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)
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)
Eldrup, A.B.; Soleymanzadeh, F.; Taylor, S.J.; Muegge, I.; Farrow, N.A.; Joseph, D.; McKellop, K.; Man, C.C.; Kukulka, A.; De Lombaert, S.
Structure-based optimization of arylamides as inhibitors of soluble epoxide hydrolase
J. Med. Chem.
52
5880-5895
2009
Homo sapiens (P34913), Homo sapiens, Rattus norvegicus (P80299)
Koeners, M.; Wesseling, S.; Ulu, A.; Sepúlveda, R.; Morisseau, C.; Braam, B.; Hammock, B.; Joles, J.
Soluble epoxide hydrolase in the generation and maintenance of high blood pressure in spontaneously hypertensive rats
Am. J. Physiol. Endocrinol. Metab.
300
691-698
2011
Rattus norvegicus
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
Qamar, W.; Khan, R.; Khan, A.Q.; Rehman, M.U.; Lateef, A.; Tahir, M.; Ali, F.; Sultana, S.
Alleviation of lung injury by glycyrrhizic acid in benzo(a)pyrene exposed rats: Probable role of soluble epoxide hydrolase and thioredoxin reductase
Toxicology
291
25-31
2011
Rattus norvegicus
Thalji, R.K.; McAtee, J.J.; Belyanskaya, S.; Brandt, M.; Brown, G.D.; Costell, M.H.; Ding, Y.; Dodson, J.W.; Eisennagel, S.H.; Fries, R.E.; Gross, J.W.; Harpel, M.R.; Holt, D.A.; Israel, D.I.; Jolivette, L.J.; Krosky, D.; Li, H.; Lu, Q.; Mandichak, T.; Roethke, T.; Schnackenberg, C.G.; Schwartz, B.; Shewchuk, L.M.
Discovery of 1-(1,3,5-triazin-2-yl)piperidine-4-carboxamides as inhibitors of soluble epoxide hydrolase
Bioorg. Med. Chem. Lett.
23
3584-3588
2013
Rattus norvegicus
Lee, K.S.; Liu, J.Y.; Wagner, K.M.; Pakhomova, S.; Dong, H.; Morisseau, C.; Fu, S.H.; Yang, J.; Wang, P.; Ulu, A.; Mate, C.A.; Nguyen, L.V.; Hwang, S.H.; Edin, M.L.; Mara, A.A.; Wulff, H.; Newcomer, M.E.; Zeldin, D.C.; Hammock, B.D.
Optimized inhibitors of soluble epoxide hydrolase improve in vitro target residence time and in vivo efficacy
J. Med. Chem.
57
7016-7030
2014
Rattus norvegicus, Homo sapiens (P34913), Homo sapiens
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)
Takai, K.; Chiyo, N.; Nakajima, T.; Nariai, T.; Ishikawa, C.; Nakatani, S.; Ikeno, A.; Yamamoto, S.; Sone, T.
Three-dimensional rational approach to the discovery of potent substituted cyclopropyl urea soluble epoxide hydrolase inhibitors
Bioorg. Med. Chem. Lett.
25
1705-1708
2015
Homo sapiens (P34913), Homo sapiens, Rattus norvegicus (P80299)
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