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Literature summary for 3.5.1.99 extracted from

  • Alapafuja, S.O.; Nikas, S.P.; Bharathan, I.T.; Shukla, V.G.; Nasr, M.L.; Bowman, A.L.; Zvonok, N.; Li, J.; Shi, X.; Engen, J.R.; Makriyannis, A.
    Sulfonyl fluoride inhibitors of fatty acid amide hydrolase (2012), J. Med. Chem., 55, 10074-10089.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine there is significant therapeutic potential for FAAH inhibitors as analgesic, neuroprotective, anti-inflammatory and anti-anxiety drugs, and as agents for the treatment of metabolic and sleep disorders Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of N-terminal maltose-binding protein fusion enzyme in CHO cells Homo sapiens
recombinant expression of transmembrane domain-deleted rat enzyme in Escherichia coli Rattus norvegicus

Inhibitors

Inhibitors Comment Organism Structure
(6E,9E,12E,15E)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-one
-
Rattus norvegicus
3'-carbamoylbiphenyl-3-yl cyclohexylcarbamate irreversible inhibitor Homo sapiens
3-phenylpropane-1-sulfonyl fluoride
-
Rattus norvegicus
4-(4-benzyloxyphenoxy)butanesulfonyl fluoride
-
Rattus norvegicus
4-phenylbutane-1-sulfonyl fluoride
-
Rattus norvegicus
5-(4-benzyloxyphenyl)pentanesulfonyl fluoride
-
Rattus norvegicus
5-(4-hydroxyphenyl)pentanesulfonyl fluoride i.e. AM3506, irreversible inhibitor for both the rat and the human enzyme, that covalently modifies the enzyme Homo sapiens
5-(4-hydroxyphenyl)pentanesulfonyl fluoride i.e. AM3506, irreversible inhibitor for both the rat and the human enzyme Rattus norvegicus
5-phenylpentane-1-sulfonyl fluoride
-
Rattus norvegicus
6-phenylhexane-1-sulfonyl fluoride
-
Rattus norvegicus
7-(2-benzyloxyphenyl)heptanesulfonyl fluoride
-
Rattus norvegicus
7-(2-hydroxyphenyl)heptanesulfonyl fluoride
-
Rattus norvegicus
7-(3-benzyloxyphenyl)heptanesulfonyl fluoride
-
Rattus norvegicus
7-(3-hydroxyphenyl)heptanesulfonyl fluoride
-
Rattus norvegicus
7-(4-benzyloxyphenyl)heptane-1-sulfonic acid methyl ester
-
Rattus norvegicus
7-(4-benzyloxyphenyl)heptanesulfonyl fluoride
-
Rattus norvegicus
7-(4-hydroxyphenyl)heptanesulfonyl fluoride
-
Rattus norvegicus
7-phenyl-1-[5-(pyridin-2-yl)-1,3-oxazol-2-yl]heptan-1-one reversible inhibitor Homo sapiens
7-phenylheptane-1-sulfonyl fluoride
-
Rattus norvegicus
8-phenyloctane-1-sulfonyl fluoride
-
Rattus norvegicus
hexadecyl sulfonylfluoride i.e. AM374, is a potent irreversible in vitro and in vivo inhibitor of fatty acid amide hydrolase Homo sapiens
hexadecyl sulfonylfluoride i.e. AM374, is a potent in vitro and in vivo inhibitor of fatty acid amide hydrolase Rattus norvegicus
methyl arachidonoyl fluorophosphonate
-
Homo sapiens
methyl arachidonoyl fluorophosphonate
-
Rattus norvegicus
additional information sulfonyl fluoride inhibitors of fatty acid amide hydrolase, structure-activity relationship, docking and molecular modeling, overview Homo sapiens
additional information sulfonyl fluoride inhibitors of fatty acid amide hydrolase, structure-activity relationship, docking and molecular modeling, overview Rattus norvegicus
phenylmethane sulfonyl fluoride irreversible inhibition Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
64391
-
x * 64391, recombinant transmembrane domain-deleted enzyme mutant, mass spectrometry Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
anandamide + H2O Rattus norvegicus
-
ethanolamine + arachidonic acid
-
?
anandamide + H2O Homo sapiens
-
ethanolamine + arachidonic acid
-
?
oleamide + H2O Rattus norvegicus
-
oleic acid + NH3
-
?
oleamide + H2O Homo sapiens
-
oleic acid + NH3
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens O00519
-
-
Rattus norvegicus P97612
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
anandamide + H2O
-
Rattus norvegicus ethanolamine + arachidonic acid
-
?
anandamide + H2O
-
Homo sapiens ethanolamine + arachidonic acid
-
?
arachidonyl-7-amino-4-methylcoumarin amide + H2O fluorogenic substrate Rattus norvegicus arachidonic acid + 7-amino-4-methylcoumarin
-
?
arachidonyl-7-amino-4-methylcoumarin amide + H2O fluorogenic substrate Homo sapiens arachidonic acid + 7-amino-4-methylcoumarin
-
?
oleamide + H2O
-
Rattus norvegicus oleic acid + NH3
-
?
oleamide + H2O
-
Homo sapiens oleic acid + NH3
-
?

Subunits

Subunits Comment Organism
? x * 64391, recombinant transmembrane domain-deleted enzyme mutant, mass spectrometry Rattus norvegicus

Synonyms

Synonyms Comment Organism
FAAH
-
Rattus norvegicus
FAAH
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Rattus norvegicus
25
-
assay at Homo sapiens

pH Optimum

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

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000012
-
pH 7.4, 25°C Rattus norvegicus 4-(4-benzyloxyphenoxy)butanesulfonyl fluoride
0.0000012
-
pH 7.4, 25°C Rattus norvegicus 7-(2-hydroxyphenyl)heptanesulfonyl fluoride
0.0000015
-
pH 7.4, 25°C Rattus norvegicus 5-(4-benzyloxyphenyl)pentanesulfonyl fluoride
0.0000022
-
pH 7.4, 25°C Rattus norvegicus 7-(4-hydroxyphenyl)heptanesulfonyl fluoride
0.0000025
-
pH 7.4, 25°C Rattus norvegicus 7-(3-hydroxyphenyl)heptanesulfonyl fluoride
0.0000028
-
pH 7.4, 25°C Rattus norvegicus 5-(4-hydroxyphenyl)pentanesulfonyl fluoride
0.0000036
-
pH 7.4, 25°C Rattus norvegicus 7-(3-benzyloxyphenyl)heptanesulfonyl fluoride
0.0000037
-
pH 7.4, 25°C Rattus norvegicus 7-(4-benzyloxyphenyl)heptanesulfonyl fluoride
0.0000043
-
pH 7.4, 25°C Rattus norvegicus 7-(2-benzyloxyphenyl)heptanesulfonyl fluoride
0.0000051
-
pH 7.4, 25°C Homo sapiens 5-(4-hydroxyphenyl)pentanesulfonyl fluoride
0.000037
-
pH 7.4, 25°C Rattus norvegicus 7-phenylheptane-1-sulfonyl fluoride
0.000038
-
pH 7.4, 25°C Rattus norvegicus 6-phenylhexane-1-sulfonyl fluoride
0.00005
-
pH 7.4, 25°C Rattus norvegicus 5-phenylpentane-1-sulfonyl fluoride
0.000088
-
pH 7.4, 25°C Rattus norvegicus 4-phenylbutane-1-sulfonyl fluoride
0.000176
-
pH 7.4, 25°C Rattus norvegicus 8-phenyloctane-1-sulfonyl fluoride
0.000205
-
pH 7.4, 25°C Rattus norvegicus 3-phenylpropane-1-sulfonyl fluoride
0.000269
-
pH 7.4, 25°C Rattus norvegicus 7-(4-benzyloxyphenyl)heptane-1-sulfonic acid methyl ester

General Information

General Information Comment Organism
malfunction enzyme inhibition and deficiency causes increased central and peripheral neuronal levels of anandamide and other FAAs producing physiological effects including analgesia, apoptosis in various cancer cells, 12-14 modulation of memory processes, neuroprotection, epilepsy, feeding, and prevention of neurotoxicity of the human amyloid-beta peptide in Alzheimer's disease. Also anti-depressant, anxiolytic, antiinflammatory, anti-hypertensive, gastrointestinal and sleep-inducing effects are observed Homo sapiens
additional information the mammalian enzyme is in the amidase signature (AS) family bearing the unusual Ser-Ser-Lys catalytic triad Rattus norvegicus
additional information the mammalian enzyme is in the amidase signature (AS) family bearing the unusual Ser-Ser-Lys catalytic triad Homo sapiens
physiological function the enzyme degrades and inactivates members of the fatty acid amide family of endogenous signaling lipids, including anandamide and oleamide. Anandamide binds and activates the CB1 and CB2 cannabinoid receptors, the molecular targets of plant-derived (-)-DELTA9-terahydrocannabinol, while oleamide induces physiological sleep and modulates serotonergic systems and GABAergic transmission Homo sapiens
physiological function the enzyme degrades and inactivates members of the fatty acid amide family of endogenous signaling lipids, including anandamide and oleamide. Anandamide binds and activates the CB1 and CB2 cannabinoid receptors, the molecular targets of plant-derived (?)-DELTA9-terahydrocannabinol, while oleamide induces physiological sleep and modulates serotonergic systems and GABAergic transmission Rattus norvegicus