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Literature summary extracted from

  • Bandiera, T.; Ponzano, S.; Piomelli, D.
    Advances in the discovery of N-acylethanolamine acid amidase inhibitors (2014), Pharmacol. Res., 86, 11-17.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.5.1.60 drug development the enzyme is a target for drug design Homo sapiens
3.5.1.60 drug development the enzyme is a target for drug design Rattus norvegicus
3.5.1.60 medicine modulation of the tissue levels of palmitoylethanolamide by inhibition of enzymes responsible for the breakdown of this lipid mediator, including the N-acylethanolamine acid amidase, may represent therefore a therapeutic strategy for the treatment of pain and inflammation Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.5.1.60 recombinant overexpression in HEK-293 cell membranes Homo sapiens
3.5.1.60 recombinant overexpression in HEK-293 cell membranes Rattus norvegicus

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.5.1.60 (S)-2-oxo-3-oxetanyl-carbamic acid benzyl ester a serine-derived beta-lactone, weak inhibition of rat lung enzyme, structure-activity relationship studies confirm that the ability of the compound to inhibit the enzyme depends on the beta-lactone ring, rather than the carbamate fragment, because analogues lacking the beta-lactone moiety are devoid of inhibitory activity Rattus norvegicus
3.5.1.60 ([1,1'-biphenyl]-4-yl)methyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate inhibition through a rapid and noncompetitive mechanism, partially reversible inhibition. The compound reacts with the catalytically active N-terminal Cys126 of human enzyme to form a thioester bond Homo sapiens
3.5.1.60 ([1,1'-biphenyl]-4-yl)methyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate modulates nociceptive responses in mice by blocking enzyme-mediated fattyacid ethanolamide degradation and restoring fattyacid ethanolamide signaling at PPAR-alpha Mus musculus
3.5.1.60 ([1,1'-biphenyl]-4-yl)methyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate reversible inhibition, modulates nociceptive responses in rats by blocking enzyme-mediated fatty acid ethanolamide degradation and restoring fattyacid ethanolamide signaling at PPAR-alpha Rattus norvegicus
3.5.1.60 1-hexadecanoylpyrrolidine weak inhibition Rattus norvegicus
3.5.1.60 1-isothiocyanatopentadecane a potent, competitive, selective, and reversible inhibitor Homo sapiens
3.5.1.60 3-(benzyloxy)propyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Homo sapiens
3.5.1.60 3-(benzyloxy)propyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Rattus norvegicus
3.5.1.60 3-([1,1'-biphenyl]-4-yl)-1-(pyrrolidin-1-yl)propan-1-one
-
 Mus musculus
3.5.1.60 3-([1,1'-biphenyl]-4-yl)-1-(pyrrolidin-1-yl)propan-1-one
-
 Rattus norvegicus
3.5.1.60 5-cyclohexylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Homo sapiens
3.5.1.60 5-cyclohexylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Rattus norvegicus
3.5.1.60 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Homo sapiens
3.5.1.60 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Rattus norvegicus
3.5.1.60 benzyl [(2R,3S)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Rattus norvegicus
3.5.1.60 benzyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
-
 Rattus norvegicus
3.5.1.60 cyclobutanol 41% inhibition at 0.05 mM Homo sapiens
3.5.1.60 Cyclopentanol 85% inhibition at 0.05 mM Homo sapiens
3.5.1.60 cyclopentyl hexadecanoate competitive inhibition Homo sapiens
3.5.1.60 additional information no or poor inhibition by N-[(3R)-2-oxo-3-oxetanyl]-3-phenylpropanamide Mus musculus
3.5.1.60 additional information amines with a long alkyl chain, in particular alkyl amines with a chain length of 14 or15 carbon atoms, and of glycine with linearalkyl alcohols of 12-16 carbon atoms inhibit the enzyme Rattus norvegicus
3.5.1.60 N-pentadecylbenzamide a potent and selective inhibitor Rattus norvegicus
3.5.1.60 N-pentadecylcyclohexancarboxamide a potent and selective inhibitor Homo sapiens
3.5.1.60 N-pentadecylcyclohexancarboxamide a potent and selective inhibitor, reversible and non-competitive inhibition mechanism Rattus norvegicus
3.5.1.60 N-[(2R,3S)-2-methyl-4-oxooxetan-3-yl]-3-phenylpropanamide very low inhibition Rattus norvegicus
3.5.1.60 N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]-3-phenylpropanamide
-
 Rattus norvegicus
3.5.1.60 N-[(3R)-2-oxo-3-oxetanyl]-3-phenylpropanamide weak inhibition Rattus norvegicus
3.5.1.60 N-[(3S)-2-oxo-3-oxetanyl]-3-phenylpropanamide noncompetitive inhibition, the compound can be used as a tool to investigate the effect of enzyme inhibition on inflammatory cells. The (S)-stereochemistry at the alpha-carbon of the beta-lactone ring is important for potent enzyme NAAA inhibition Mus musculus
3.5.1.60 N-[(3S)-2-oxo-3-oxetanyl]-3-phenylpropanamide noncompetitive inhibition, the compound can be used as a tool to investigate the effect of enzyme inhibition on inflammatory cells. The (S) stereochemistry at the alpha-carbon of the beta-lactone ring is important for potent enzyme NAAA inhibition Rattus norvegicus
3.5.1.60 N-[(3S)-2-oxooxetan-3-yl]heptanamide
-
 Rattus norvegicus
3.5.1.60 N-[(3S)-2-oxooxetan-3-yl]naphthalene-2-carboxamide
-
 Rattus norvegicus
3.5.1.60 N-[(3S)-2-oxooxetan-3-yl][1,1'-biphenyl]-4-carboxamide
-
 Rattus norvegicus
3.5.1.60 palmitic acid retro-amides N-pentadecylbenzamide a potent and selective inhibitor Homo sapiens
3.5.1.60 pentadecylamine competitive inhibition Rattus norvegicus
3.5.1.60 tridecyl glycine competitive inhibition Rattus norvegicus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.5.1.60 additional information Rattus norvegicus N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or mono-unsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide ?
-
 ?
3.5.1.60 additional information Mus musculus N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide ?
-
 ?
3.5.1.60 additional information Homo sapiens N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide ?
-
 ?
3.5.1.60 oleoylethanolamide + H2O Mus musculus
-
 oleic acid + ethanolamine
-
 ?
3.5.1.60 oleoylethanolamide + H2O Homo sapiens
-
 oleic acid + ethanolamine
-
 ?
3.5.1.60 oleoylethanolamide + H2O Rattus norvegicus
-
 oleic acid + ethanolamine
-
 ?
3.5.1.60 palmitoylethanolamide + H2O Mus musculus
-
 palmitic acid + ethanolamine
-
 ?
3.5.1.60 palmitoylethanolamide + H2O Homo sapiens
-
 palmitic acid + ethanolamine
-
 ?
3.5.1.60 palmitoylethanolamide + H2O Rattus norvegicus
-
 palmitic acid + ethanolamine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.5.1.60 Homo sapiens Q02083
-
-
3.5.1.60 Mus musculus
-
-
-
3.5.1.60 Rattus norvegicus Q5KTC7
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.5.1.60 alveolar macrophage
-
 Rattus norvegicus
-
3.5.1.60 lung
-
 Rattus norvegicus
-
3.5.1.60 macrophage
-
 Mus musculus
-
3.5.1.60 RAW-264.7 cell
-
 Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.5.1.60 additional information N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or mono-unsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide Rattus norvegicus ?
-
 ?
3.5.1.60 additional information N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide Mus musculus ?
-
 ?
3.5.1.60 additional information N-acylethanolamine acid amidase is a cysteine amidase that hydrolyzes saturated or monounsaturated fatty acid ethanolamides, such as palmitoylethanolamide and oleoylethanolamide Homo sapiens ?
-
 ?
3.5.1.60 oleoylethanolamide + H2O
-
 Mus musculus oleic acid + ethanolamine
-
 ?
3.5.1.60 oleoylethanolamide + H2O
-
 Homo sapiens oleic acid + ethanolamine
-
 ?
3.5.1.60 oleoylethanolamide + H2O
-
 Rattus norvegicus oleic acid + ethanolamine
-
 ?
3.5.1.60 palmitoylethanolamide + H2O
-
 Mus musculus palmitic acid + ethanolamine
-
 ?
3.5.1.60 palmitoylethanolamide + H2O
-
 Homo sapiens palmitic acid + ethanolamine
-
 ?
3.5.1.60 palmitoylethanolamide + H2O
-
 Rattus norvegicus palmitic acid + ethanolamine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.5.1.60 N-acylethanolamine acid amidase
-
 Mus musculus
3.5.1.60 N-acylethanolamine acid amidase
-
 Homo sapiens
3.5.1.60 N-acylethanolamine acid amidase
-
 Rattus norvegicus
3.5.1.60 NAAA
-
 Mus musculus
3.5.1.60 NAAA
-
 Homo sapiens
3.5.1.60 NAAA
-
 Rattus norvegicus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.5.1.60 5
-
-
 Rattus norvegicus

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3.5.1.60 0.000007
-
 pH and temperature not specified in the publication Homo sapiens ([1,1'-biphenyl]-4-yl)methyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
3.5.1.60 0.000007
-
 pH and temperature not specified in the publication Rattus norvegicus ([1,1'-biphenyl]-4-yl)methyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
3.5.1.60 0.000007
-
 pH and temperature not specified in the publication Homo sapiens 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
3.5.1.60 0.000115
-
 pH and temperature not specified in the publication Rattus norvegicus N-[(3S)-2-oxooxetan-3-yl][1,1'-biphenyl]-4-carboxamide
3.5.1.60 0.00016
-
 pH and temperature not specified in the publication Rattus norvegicus N-[(3S)-2-oxooxetan-3-yl]naphthalene-2-carboxamide
3.5.1.60 0.00035 0.0006 pH and temperature not specified in the publication Homo sapiens 1-isothiocyanatopentadecane
3.5.1.60 0.00042
-
 pH and temperature not specified in the publication Rattus norvegicus N-[(3S)-2-oxo-3-oxetanyl]-3-phenylpropanamide
3.5.1.60 0.00046
-
 pH and temperature not specified in the publication Rattus norvegicus N-[(3S)-2-oxooxetan-3-yl]heptanamide
3.5.1.60 0.001
-
 pH and temperature not specified in the publication Rattus norvegicus benzyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
3.5.1.60 0.00212
-
 pH and temperature not specified in the publication Rattus norvegicus 3-([1,1'-biphenyl]-4-yl)-1-(pyrrolidin-1-yl)propan-1-one
3.5.1.60 0.00296
-
 pH and temperature not specified in the publication Rattus norvegicus (S)-2-oxo-3-oxetanyl-carbamic acid benzyl ester
3.5.1.60 0.0032
-
 pH and temperature not specified in the publication Rattus norvegicus N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]-3-phenylpropanamide
3.5.1.60 0.0045
-
 pH and temperature not specified in the publication Rattus norvegicus N-pentadecylcyclohexancarboxamide
3.5.1.60 0.0057
-
 pH and temperature not specified in the publication Rattus norvegicus pentadecylamine
3.5.1.60 0.006
-
 pH and temperature not specified in the publication Rattus norvegicus N-[(3R)-2-oxo-3-oxetanyl]-3-phenylpropanamide
3.5.1.60 0.0083
-
 pH and temperature not specified in the publication Rattus norvegicus N-pentadecylbenzamide
3.5.1.60 0.01
-
 pH and temperature not specified in the publication Homo sapiens cyclopentyl hexadecanoate
3.5.1.60 0.01
-
 above, pH and temperature not specified in the publication Rattus norvegicus benzyl [(2R,3S)-2-methyl-4-oxooxetan-3-yl]carbamate
3.5.1.60 0.025
-
 pH and temperature not specified in the publication Rattus norvegicus 1-hexadecanoylpyrrolidine
3.5.1.60 0.05
-
 pH and temperature not specified in the publication Rattus norvegicus 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate
3.5.1.60 0.1
-
 above, pH and temperature not specified in the publication Rattus norvegicus N-[(2R,3S)-2-methyl-4-oxooxetan-3-yl]-3-phenylpropanamide

General Information

EC Number General Information Comment Organism
3.5.1.60 evolution the enzyme is a cysteine hydrolase belonging to the N-terminalnucleophile (Ntn) family of enzymes Mus musculus
3.5.1.60 evolution the enzyme is a cysteine hydrolase belonging to the N-terminalnucleophile (Ntn) family of enzymes Homo sapiens
3.5.1.60 evolution the enzyme is a cysteine hydrolase belonging to the N-terminalnucleophile (Ntn) family of enzymes Rattus norvegicus
3.5.1.60 malfunction enzyme inhibitors may attenuate heat hyperalgesia and mechanical allodynia caused by local inflammation or nerve damage in animal models of pain and inflammation Homo sapiens
3.5.1.60 malfunction enzyme inhibitors may attenuate heat hyperalgesia and mechanical allodynia caused by local inflammation or nerve damage in animal models of pain and inflammation Rattus norvegicus
3.5.1.60 physiological function the enzyme intracellularly breaks down the analgesic and anti-inflammatory mediator palmitoylethanolamide Mus musculus
3.5.1.60 physiological function the enzyme intracellularly breaks down the analgesic and anti-inflammatory mediator palmitoylethanolamide Homo sapiens
3.5.1.60 physiological function the enzyme intracellularly breaks down the analgesic and anti-inflammatory mediator palmitoylethanolamide Rattus norvegicus