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Literature summary extracted from

  • Pizzirani, D.; Bach, A.; Realini, N.; Armirotti, A.; Mengatto, L.; Bauer, I.; Girotto, S.; Pagliuca, C.; De Vivo, M.; Summa, M.; Ribeiro, A.; Piomelli, D.
    Benzoxazolone carboxamides: potent and systemically active inhibitors of intracellular acid ceramidase (2015), Angew. Chem. Int. Ed. Engl., 54, 485-489.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
3.5.1.23 medicine because of its central role in the ceramide metabolism, the enzyme may offer a novel molecular target in disorders with dysfunctional ceramide-mediated signaling Homo sapiens
3.5.1.23 medicine because of its central role in the ceramide metabolism, the enzyme may offer a novel molecular target in disorders with dysfunctional ceramide-mediated signaling Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.5.1.23 2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Homo sapiens
3.5.1.23 2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Mus musculus
3.5.1.23 6-(4-fluorophenyl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Homo sapiens
3.5.1.23 6-(4-fluorophenyl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide} in vivo plasma pharmacokinetic profile in mice, overview Mus musculus
3.5.1.23 6-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Homo sapiens
3.5.1.23 6-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Mus musculus
3.5.1.23 additional information a class of benzoxazolone carboxamides act as the first potent and systemically active inhibitors of the acid ceramidase. Prototype members of this class inhibit the enzyme with low nanomolar potency by covalent binding to the catalytic cysteine. No inhibition by N-methyl-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide, 4-phenylbutyl 2-oxo-1,3-benzoxazole-3(2H)-carboxylate, and 3-(6-phenylhexanoyl)-1,3-benzoxazol-2(3H)-one, while 2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carbothioamide is unstable Homo sapiens
3.5.1.23 additional information a class of benzoxazolone carboxamides act as the first potent and systemically active inhibitors of the acid ceramidase. Prototype members of this class inhibit the enzyme with low nanomolar potency by covalent binding to the catalytic cysteine. No inhibition by N-methyl-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide, 4-phenylbutyl 2-oxo-1,3-benzoxazole-3(2H)-carboxylate, and 3-(6-phenylhexanoyl)-1,3-benzoxazol-2(3H)-one, while 2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carbothioamide is unstable Mus musculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.5.1.23 N-acylsphingosine + H2O Homo sapiens the carboxylate is a fatty acid carboxylate + sphingosine
-
 ?
3.5.1.23 N-acylsphingosine + H2O Mus musculus the carboxylate is a fatty acid carboxylate + sphingosine
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.5.1.23 Homo sapiens Q13510
-
-
3.5.1.23 Mus musculus Q9WV54
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.5.1.23 brain
-
 Mus musculus
-
3.5.1.23 colon
-
 Mus musculus
-
3.5.1.23 colon adenocarcinoma cell
-
 Homo sapiens
-
3.5.1.23 heart
-
 Mus musculus
-
3.5.1.23 hippocampus
-
 Mus musculus
-
3.5.1.23 kidney
-
 Mus musculus
-
3.5.1.23 liver
-
 Mus musculus
-
3.5.1.23 lung
-
 Mus musculus
-
3.5.1.23 pancreas
-
 Mus musculus
-
3.5.1.23 RAW-264.7 cell
-
 Mus musculus
-
3.5.1.23 SW-403 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.5.1.23 N-acylsphingosine + H2O the carboxylate is a fatty acid Homo sapiens carboxylate + sphingosine
-
 ?
3.5.1.23 N-acylsphingosine + H2O the carboxylate is a fatty acid Mus musculus carboxylate + sphingosine
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.5.1.23 acid ceramidase
-
 Homo sapiens
3.5.1.23 acid ceramidase
-
 Mus musculus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.5.1.23 37
-
 assay at Homo sapiens
3.5.1.23 37
-
 assay at Mus musculus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.5.1.23 7.4
-
 assay at Homo sapiens
3.5.1.23 7.4
-
 assay at Mus musculus

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
3.5.1.23 0.000031
-
 pH 7.4, 37°C Homo sapiens 6-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
3.5.1.23 0.000064
-
 pH 7.4, 37°C Homo sapiens 2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
3.5.1.23 0.000079
-
 pH 7.4, 37°C Homo sapiens 6-(4-fluorophenyl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide

General Information

EC Number General Information Comment Organism
3.5.1.23 physiological function ceramide hydrolysis by acid ceramidase stops the biological activity of ceramides and influences survival and function of normal and neoplastic cells Homo sapiens
3.5.1.23 physiological function ceramide hydrolysis by acid ceramidase stops the biological activity of ceramides and influences survival and function of normal and neoplastic cells Mus musculus