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Literature summary for 3.5.1.23 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
Search for more literature for 3.5.1.23

Application

Application Comment Organism
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
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

Inhibitors Comment Organism Structure
2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Homo sapiens
2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Mus musculus
6-(4-fluorophenyl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Homo sapiens
6-(4-fluorophenyl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide} in vivo plasma pharmacokinetic profile in mice, overview Mus musculus
6-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Homo sapiens
6-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3(2H)-carboxamide
-
 Mus musculus
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
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)

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

Organism

Organism UniProt Comment Textmining
Homo sapiens Q13510
-
-
Mus musculus Q9WV54
-
-

Source Tissue

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

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
acid ceramidase
-
 Homo sapiens
acid ceramidase
-
 Mus musculus

Temperature Optimum [°C]

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

pH Optimum

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

IC50 Value

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

General Information Comment Organism
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
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