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Literature summary for 3.3.2.9 extracted from

  • Toselli, F.; Fredenwall, M.; Svensson, P.; Li, X.Q.; Johansson, A.; Weidolf, L.; Hayes, M.A.
    Oxetane substrates of human microsomal epoxide hydrolase (2017), Drug Metab. Dispos., 45, 966-973 .
    View publication on PubMed
Search for more literature for 3.3.2.9

Activating Compound

Activating Compound Comment Organism Structure
additional information minimally altering the structural elements in the immediate vicinity of the oxetane can greatly modulate the efficiency of hydrolytic ring cleavage. In particular, higher pKa in the vicinity of the oxetane and an increased distance between the oxetane ring and the benzylic nitrogen improve reaction rate, which is further enhanced by the presence of methyl groups near or on the oxetane Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
valpromide
-
 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information Michaelis-Menten-type kinetics for native (using liver microsomes) and recombinant enzymes with different substrates Homo sapiens
0.026
-
 [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone pH 7.4, 37°C, liver microsomes Homo sapiens
0.027
-
 [3-[4-([((3-methyloxetan-3-yl)methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone pH 7.4, 37°C, liver microsomes Homo sapiens
0.028
-
 [3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone pH 7.4, 37°C, liver microsomes Homo sapiens
0.047
-
 [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone pH 7.4, 37°C, recombinant enzyme Homo sapiens
0.05
-
 [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone pH 7.4, 37°C, recombinant enzyme Homo sapiens
0.051
-
 [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone pH 7.4, 37°C, liver microsomes Homo sapiens
0.067
-
 [3-[4-([((3-methyloxetan-3-yl)methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone pH 7.4, 37°C, recombinant enzyme Homo sapiens
0.089
-
 [3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone pH 7.4, 37°C, recombinant enzyme Homo sapiens
0.139
-
 2-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine pH 7.4, 37°C, liver microsomes Homo sapiens
0.352
-
 1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine pH 7.4, 37°C, liver microsomes Homo sapiens
0.684
-
 2-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine pH 7.4, 37°C, recombinant enzyme Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome
-
 Homo sapiens
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens oxetanes are a nonepoxide class of substrates for human mEH, which is known to catalyze the hydrolytic ring opening of electrophilic and potentially toxic epoxide-containing drugs, drug metabolites, and exogenous organochemicals ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P07099
-
-

Source Tissue

Source Tissue Comment Organism Textmining
hepatocyte
-
 Homo sapiens
-
liver
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(R)-styrene oxide + H2O
-
 Homo sapiens (1R)-1-phenylethane-1,2-diol
-
 ?
1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine + H2O
-
 Homo sapiens 2-([[(4-methoxyphenyl)methyl](methyl)amino]methyl)-2-methylpropane-1,3-diol
-
 ir
1-[3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]ethan-1-one + H2O
-
 Homo sapiens 1-[3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl]ethan-1-one [3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl]ethan-1-one ir
2-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine + H2O
-
 Homo sapiens 2-([[2-(4-methoxyphenyl)ethyl](methyl)amino]methyl)-2-methylpropane-1,3-diol
-
 ir
cis-stilbene oxide + H2O
-
 Homo sapiens (1R,2R)-1,2-diphenylethane-1,2-diol
-
 ?
additional information oxetanes are a nonepoxide class of substrates for human mEH, which is known to catalyze the hydrolytic ring opening of electrophilic and potentially toxic epoxide-containing drugs, drug metabolites, and exogenous organochemicals Homo sapiens ?
-
 ?
additional information no activity with [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[methyl(oxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone, [5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[(3-methyloxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone, 2-(4-methoxyphenyl)-N-[(3-methyloxetan-3-yl)methyl]ethan-1-amine, and 2-(4-methoxyphenyl)-N-methyl-N-[(oxetan-3-yl)methyl]ethan-1-amine Homo sapiens ?
-
 ?
[3-(4-[[(oxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone + H2O
-
 Homo sapiens [3-(4-[[(1,3-dihydroxypropan-2-yl)amino]methyl]phenoxy)azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
-
 ir
[3-[4-([((3-methyloxetan-3-yl)methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone + H2O
-
 Homo sapiens [3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
-
 ir
[3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone + H2O
-
 Homo sapiens [3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl](5-phenyl-1,3,4-oxadiazol-2-yl)methanone
-
 ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-(4-[[(oxetan-3-yl)amino]methyl]phenoxy)azetidin-1-yl]methanone + H2O
-
 Homo sapiens [3-(4-[[(1,3-dihydroxypropan-2-yl)amino]methyl]phenoxy)azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
 ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([methyl[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone + H2O
-
 Homo sapiens [3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl](methyl)amino]methyl)phenoxy]azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
 ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(3-methyloxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone + H2O
-
 Homo sapiens [3-[4-([[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl]amino]methyl)phenoxy]azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
 ir
[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl][3-[4-([[(oxetan-3-yl)methyl]amino]methyl)phenoxy]azetidin-1-yl]methanone + H2O
-
 Homo sapiens [3-[4-([[3-hydroxy-2-(hydroxymethyl)propyl]amino]methyl)phenoxy]azetidin-1-yl][5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]methanone
-
 ir

Synonyms

Synonyms Comment Organism
mEH
-
 Homo sapiens
Microsomal epoxide hydrolase
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

General Information

General Information Comment Organism
physiological function in human liver fractions and hepatocytes, oxetane hydrolysis by mEH is the only oxetane ring-opening metabolic route, with no contribution from soluble epoxide hydrolase (sEH, EC 3.3.2.10) or from cytochrome P450-catalyzed oxidation Homo sapiens