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Literature summary for 3.5.1.60 extracted from
- Advances in the discovery of N-acylethanolamine acid amidase inhibitors (2014), Pharmacol. Res., 86, 11-17.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | the enzyme is a target for drug design | Homo sapiens |
| drug development | the enzyme is a target for drug design | Rattus norvegicus |
| 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)
| Cloned (Comment) | Organism |
|---|---|
| recombinant overexpression in HEK-293 cell membranes | Homo sapiens |
| recombinant overexpression in HEK-293 cell membranes | Rattus norvegicus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| (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 |  |
| ([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 | |
| ([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 | |
| ([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 | |
| 1-hexadecanoylpyrrolidine | weak inhibition | Rattus norvegicus | |
| 1-isothiocyanatopentadecane | a potent, competitive, selective, and reversible inhibitor | Homo sapiens | |
| 3-(benzyloxy)propyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Homo sapiens | |
| 3-(benzyloxy)propyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Rattus norvegicus | |
| 3-([1,1'-biphenyl]-4-yl)-1-(pyrrolidin-1-yl)propan-1-one | - |
Mus musculus | |
| 3-([1,1'-biphenyl]-4-yl)-1-(pyrrolidin-1-yl)propan-1-one | - |
Rattus norvegicus | |
| 5-cyclohexylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Homo sapiens | |
| 5-cyclohexylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Rattus norvegicus | |
| 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Homo sapiens | |
| 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Rattus norvegicus | |
| benzyl [(2R,3S)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Rattus norvegicus | |
| benzyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | - |
Rattus norvegicus | |
| cyclobutanol | 41% inhibition at 0.05 mM | Homo sapiens | |
| Cyclopentanol | 85% inhibition at 0.05 mM | Homo sapiens | |
| cyclopentyl hexadecanoate | competitive inhibition | Homo sapiens | |
| additional information | no or poor inhibition by N-[(3R)-2-oxo-3-oxetanyl]-3-phenylpropanamide | Mus musculus | |
| 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 | |
| N-pentadecylbenzamide | a potent and selective inhibitor | Rattus norvegicus | |
| N-pentadecylcyclohexancarboxamide | a potent and selective inhibitor | Homo sapiens | |
| N-pentadecylcyclohexancarboxamide | a potent and selective inhibitor, reversible and non-competitive inhibition mechanism | Rattus norvegicus | |
| N-[(2R,3S)-2-methyl-4-oxooxetan-3-yl]-3-phenylpropanamide | very low inhibition | Rattus norvegicus | |
| N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]-3-phenylpropanamide | - |
Rattus norvegicus | |
| N-[(3R)-2-oxo-3-oxetanyl]-3-phenylpropanamide | weak inhibition | Rattus norvegicus | |
| 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 | |
| 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 | |
| N-[(3S)-2-oxooxetan-3-yl]heptanamide | - |
Rattus norvegicus | |
| N-[(3S)-2-oxooxetan-3-yl]naphthalene-2-carboxamide | - |
Rattus norvegicus | |
| N-[(3S)-2-oxooxetan-3-yl][1,1'-biphenyl]-4-carboxamide | - |
Rattus norvegicus | |
| palmitic acid retro-amides N-pentadecylbenzamide | a potent and selective inhibitor | Homo sapiens | |
| pentadecylamine | competitive inhibition | Rattus norvegicus | |
| tridecyl glycine | competitive inhibition | Rattus norvegicus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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 | ? | - |
? | |
| 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 | ? | - |
? | |
| 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 | ? | - |
? | |
| oleoylethanolamide + H2O | Mus musculus | - |
oleic acid + ethanolamine | - |
? | |
| oleoylethanolamide + H2O | Homo sapiens | - |
oleic acid + ethanolamine | - |
? | |
| oleoylethanolamide + H2O | Rattus norvegicus | - |
oleic acid + ethanolamine | - |
? | |
| palmitoylethanolamide + H2O | Mus musculus | - |
palmitic acid + ethanolamine | - |
? | |
| palmitoylethanolamide + H2O | Homo sapiens | - |
palmitic acid + ethanolamine | - |
? | |
| palmitoylethanolamide + H2O | Rattus norvegicus | - |
palmitic acid + ethanolamine | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q02083 | - |
- |
| Mus musculus | - |
- |
- |
| Rattus norvegicus | Q5KTC7 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| alveolar macrophage | - |
Rattus norvegicus | - |
| lung | - |
Rattus norvegicus | - |
| macrophage | - |
Mus musculus | - |
| RAW-264.7 cell | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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 | ? | - |
? | |
| 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 | ? | - |
? | |
| 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 | ? | - |
? | |
| oleoylethanolamide + H2O | - |
Mus musculus | oleic acid + ethanolamine | - |
? | |
| oleoylethanolamide + H2O | - |
Homo sapiens | oleic acid + ethanolamine | - |
? | |
| oleoylethanolamide + H2O | - |
Rattus norvegicus | oleic acid + ethanolamine | - |
? | |
| palmitoylethanolamide + H2O | - |
Mus musculus | palmitic acid + ethanolamine | - |
? | |
| palmitoylethanolamide + H2O | - |
Homo sapiens | palmitic acid + ethanolamine | - |
? | |
| palmitoylethanolamide + H2O | - |
Rattus norvegicus | palmitic acid + ethanolamine | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| N-acylethanolamine acid amidase | - |
Mus musculus |
| N-acylethanolamine acid amidase | - |
Homo sapiens |
| N-acylethanolamine acid amidase | - |
Rattus norvegicus |
| NAAA | - |
Mus musculus |
| NAAA | - |
Homo sapiens |
| NAAA | - |
Rattus norvegicus |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 5 | - |
- |
Rattus norvegicus |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 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 | |
| 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 | |
| 0.000007 | - |
pH and temperature not specified in the publication | Homo sapiens | 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | |
| 0.000115 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-[(3S)-2-oxooxetan-3-yl][1,1'-biphenyl]-4-carboxamide | |
| 0.00016 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-[(3S)-2-oxooxetan-3-yl]naphthalene-2-carboxamide | |
| 0.00035 | 0.0006 | pH and temperature not specified in the publication | Homo sapiens | 1-isothiocyanatopentadecane | |
| 0.00042 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-[(3S)-2-oxo-3-oxetanyl]-3-phenylpropanamide | |
| 0.00046 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-[(3S)-2-oxooxetan-3-yl]heptanamide | |
| 0.001 | - |
pH and temperature not specified in the publication | Rattus norvegicus | benzyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | |
| 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 | |
| 0.00296 | - |
pH and temperature not specified in the publication | Rattus norvegicus | (S)-2-oxo-3-oxetanyl-carbamic acid benzyl ester | |
| 0.0032 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-[(2S,3R)-2-methyl-4-oxooxetan-3-yl]-3-phenylpropanamide | |
| 0.0045 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-pentadecylcyclohexancarboxamide | |
| 0.0057 | - |
pH and temperature not specified in the publication | Rattus norvegicus | pentadecylamine | |
| 0.006 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-[(3R)-2-oxo-3-oxetanyl]-3-phenylpropanamide | |
| 0.0083 | - |
pH and temperature not specified in the publication | Rattus norvegicus | N-pentadecylbenzamide | |
| 0.01 | - |
pH and temperature not specified in the publication | Homo sapiens | cyclopentyl hexadecanoate | |
| 0.01 | - |
above, pH and temperature not specified in the publication | Rattus norvegicus | benzyl [(2R,3S)-2-methyl-4-oxooxetan-3-yl]carbamate | |
| 0.025 | - |
pH and temperature not specified in the publication | Rattus norvegicus | 1-hexadecanoylpyrrolidine | |
| 0.05 | - |
pH and temperature not specified in the publication | Rattus norvegicus | 5-phenylpentyl [(2S,3R)-2-methyl-4-oxooxetan-3-yl]carbamate | |
| 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
| General Information | Comment | Organism |
|---|---|---|
| evolution | the enzyme is a cysteine hydrolase belonging to the N-terminalnucleophile (Ntn) family of enzymes | Mus musculus |
| evolution | the enzyme is a cysteine hydrolase belonging to the N-terminalnucleophile (Ntn) family of enzymes | Homo sapiens |
| evolution | the enzyme is a cysteine hydrolase belonging to the N-terminalnucleophile (Ntn) family of enzymes | Rattus norvegicus |
| 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 |
| 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 |
| physiological function | the enzyme intracellularly breaks down the analgesic and anti-inflammatory mediator palmitoylethanolamide | Mus musculus |
| physiological function | the enzyme intracellularly breaks down the analgesic and anti-inflammatory mediator palmitoylethanolamide | Homo sapiens |
| physiological function | the enzyme intracellularly breaks down the analgesic and anti-inflammatory mediator palmitoylethanolamide | Rattus norvegicus |
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