Amidase

Amidases, belonging to the nitrilase superfamily, catalyze amide hydrolysis to yield carboxylic acid and ammonia. These enzymes feature a conserved AS sequence of about 130 amino acids and are pivotal in essential metabolic processes [1].

Penicillin amidase is an enzyme that cleaves the acyl side chain of penicillin, used in the production of 6-aminopenicillanic acid, as well as the resolution of racemic mixtures, synthesis of peptides and semi-synthetic β-lactam antibiotics.

ARN19702 is a selective, orally active, reversible, and brain-penetrant N-acylethanolamine acid amidase (NAAA) inhibitor with an IC50 of 230 nM for human NAAA, exhibiting a broad analgesic profile [1] [2].

Acid Ceramidase-IN-3 is an inhibitor of acid ceramidase (aCDase). It shows a pIC50 of 8.5 in enzymatic assays and a pIC50 of 6.8 in A375 melanoma cell assays for aCDase enzyme activity inhibition. Acid Ceramidase-IN-3 promotes hepatic stellate cell (HSC) inactivation, measured by dose-dependent reduction of COL1A1 and ACTA2 levels. Additionally, it inhibits aCDase activity in HSCs, facilitating their inactivation and inhibiting YAP/TAZ nuclear localization. The compound enhances the expression of dynein/kinesin-related proteins (NDE1, NDEL1, KIF3B, KIF15) while reducing the expression of proteins related to various signaling pathways (SARM1, RGAP1, PDGF-D, PDGFR-B). Acid Ceramidase-IN-3 is valuable for fibrosis disease research.

Acid Ceramidase-IN-1 is a highly effective, orally bioavailable inhibitor of acid ceramidase (AC, ASAH-1) with an IC50 of 0.166 μM and exhibits exceptional brain penetration capabilities in mice.

Acid Ceramidase-IN-2 (compound 1), an acid ceramidase inhibitor, exhibits potentially antiproliferative and cytostatic effects. It is of interest due to the overexpression of human acid ceramidase in prostate cancer cells, suggesting potential anti-tumor efficacy. The hydrolysis of Acid Ceramidase-IN-2 can be inhibited by 3 a-ketoamides: GT85, GT98, and GT99 in vitro [1].

Endoglycoceramidase II (EGCase II), an endo-β-glucosidase, catalyzes the hydrolysis of the β-glycosidic linkage between oligosaccharides and ceramides in glycosphingolipids, releasing the complete glycan from ceramide [1] [2].

Endoglycoceramidase I (EGCase I), a glycosidase frequently utilized in biochemical studies, catalyzes a transglycosylation reaction. This process involves transferring the sugar moiety of GSLs to the primary hydroxyl group of various 1-alkanols [1].

Recombinant endoglycoceramidase II (rEGCase II) is an endo-β-glucosidase that releases intact glycans from the ceramide portion of sphingolipids. It catalyzes the hydrolysis of the β-glycosidic bond between oligosaccharides and ceramide in various sphingolipids.

Recombinant endoglycoceramidase I assisted by activator II (rEGCase I assisted by Activator II) is a mixture of EGCase I and Activator II. EGCase I is a specific hydrolase ideal for comprehensive analysis of glycolipid compounds (GSLs). Activator II enhances the activity of EGCase without requiring any detergents.

Recombinant endoglycoceramidase I (rEGCase I) is a glycosidase that facilitates the hydrolysis of β-glycosidic bonds between oligosaccharides and ceramides. Additionally, it catalyzes transglycosylation reactions, transferring the sugar moiety of glycosphingolipids to the primary hydroxyl groups of various 1-alkanols.

Recombinant endoglycoceramidase II assisted by activator II is a biocatalyst and a key enzyme in new biocatalysis technology. Enzyme engineering focuses on improving the reaction kinetics, substrate selectivity, and activity under extreme conditions (such as low or high pH). By introducing stimulus-responsive modifications to these enzymes, dynamic control of activity becomes feasible.

Galactosylceramidase plays a role in the lysosomal catabolism of galactosylceramide. It can be utilized in research related to Krabbe disease.

Ceranib-2 (3-[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-4-phenyl-1H-quinolin-2-one) is an inhibitor of ceramidase with an IC50 of 28 μM in SKOV3 cells. Ceranib-2 decreases levels of sphingosine and S1P, induces cell apoptosis and exhibits anticancer activity.

Ceranib1 is an inhibitor of ceramidase. It inhibits the proliferation of ovarian cancer cells. Ceranib1 inhibits ceramidase activity toward an exogenous ceramide analog, induces the accumulation of multiple ceramide species, decreases levels of S1P and sphingosine.

Pyrazinamide (Pyrazinecarboxamide), an antimycobacterial, is utilized therapeutically as an antitubercular agent, which is a synthetic pyrazinoic acid amide derivative.

AM 374 (HDSF), a fatty acid amide hydrolase (FAAH) inhibitor, demonstrates the capacity to inhibit amidase activity, boasting an IC50 value of 13 nM. This compound is potentially applicable in neurological disease research.

LCL521 inhibits lysosomal acid sphingomyelinase (ASMase).LCL521 is an acid ceramidase (ACDase) inhibitor.

ARN14974 is a benzoxazolone carboxamide. ARN14974 is a potent inhibitor of acid ceramidase with IC50 of 79 nM[1].

D-erythro-MAPP (D-e-MAPP) is a ceramidase inhibitor, a ceramide analog with potential anticancer activity.

AA26-9 is an effective and broad-spectrum inhibitor of serine hydrolase.

Glucocerebrosidase (Glucosylceramidase; GBA), a lysosomal enzyme, catalyzes the hydrolysis of the β-glucosidic linkage in glucocerebroside (GC) to yield glucose and ceramide [1].

Lysostaphin is a potent antistaphylococcal compound that exhibits enzymatic activity through three distinct enzymes: glycylglycine endopeptidase, endo-β-N-acetyl glucosamidase, and N-acetyl muramyl-L-alanine amidase.

ARN 077 is a selective N-acylethanolamine acid amidase (NAAA) inhibitor (IC50: 7 nM for human NAAA). ARN 077 significantly increases palmitoyl ethanolamine (PEA) levels within the CNS.