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 (Penicillin acylase) is an enzyme utilized for cleaving the acyl side chains from penicillins. It facilitates the production of 6-aminopenicillanic acid and is also employed in resolving racemic mixtures, peptide synthesis, and the creation of semi-synthetic β-lactam antibiotics [1] [2] [3].

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].

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

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.

2-Chlorophenylboronic acid is a monohalogenated phenylboronic acid, which is an important pharmaceutical intermediate and is widely used in the synthesis of new drugs.2-Chlorophenylboronic acid has an inhibitory effect on fatty acid amidase with a Ki value of 0.01-1 µM, and is used in the study of depression, glaucoma, neuropathic pain, anxiety, migraine, I diabetes and gastritis. , migraine, type I diabetes and gastritis.

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.

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].

MAFP (Methyl Arachidonyl Fluorophosphonate) is an effective, active-site directed irreversible inhibitor of anandamide amidase, cPLA2, and iPLA2.

Brivaracetam (αR,4R) is a third-generation antiepileptic drug and anticonvulsant compound frequently used in combination with other antiepileptic compounds for the treatment of partial-onset seizures. It acts as a high-affinity ligand for synaptic vesicle protein 2A, reducing neurotransmitter release by binding to synaptic vesicle glycoprotein SV2A. Brivaracetam (αR,4R) is primarily metabolized into inactive metabolites through hydrolysis by amidase.

ARN14686 is an activity-based affinity probe for the detection of N-acylethanolamine acid amidase (NAAA) using click chemistry.

17-phenyl trinor Prostaglandin F2α N-ethyl amide (17-phenyl trinor PGF2α) is an F-series prostaglandin analog which has been approved for use as an ocular hypotensive drug, sold under the Allergan trade name 17-phenyl trinor PGF2α ethyl amide. Investigations in our lab have shown that 17-phenyl trinor PGF2α ethyl amide is converted by an amidase enzymatic activity in the human cornea to yield the corresponding free acid, with a conversion rate of about 25 μg/cornea/24 hours. The free acid, 17-phenyl trinor PGF2α, is a potent FP receptor agonist. 15(R)-17-phenyl trinor PGF2α is the 15-epi, or unnatural isomer of this active free acid metabolite. It has much diminished FP receptor-mediated activity

NAAA-IN-2 (Compound 9), a potent and selective inhibitor of NAAA, exhibits an IC50 of 50 nM. NAAA, a cysteine amidase, primarily breaks down the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). This compound demonstrates promise for inflammation and pain research [1].

NAAA-IN-3 (Compound 17a) is a potent and selective NAAA inhibitor with an IC50 of 50 nM. NAAA is a cysteine amidase that preferentially hydrolyzes the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). PEA is an endogenous agonist of the nuclear peroxisome proliferator-activated receptor-α (PPAR-α), a key regulator of inflammation and pain. The potential role of NAAA-IN-3 is as a therapeutic agent for the treatment of inflammation and pain.

ARN726 is a potent inhibitor of NAAA (N-acylethanolamine acid amidase) with an IC 50 of 0.073 μM which decreases the motivation for alcohol in a dose-dependent manner [1] [2].

NAAA-IN-1 (Compound 1) is a potent and selective NAAA inhibitor (IC50 = 7 nM) that can be used in inflammation and pain research. NAAA, a cysteine amidase, preferentially hydrolyzes the endogenous biolipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) [1].

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.

Clostripain (Clostridiopeptidase B), a proteolytic enzyme derived from Clostridium histolyticum, exhibits esterase, amidase, and protease activities. It is notably specific for cleaving carboxy-terminal arginine residues in proteins [1].

17-Phenyl trinor Prostaglandin F2αdiethyl amide (17-phenyl trinor PGF2αdiethyl amide) is a Prostaglandin F2α(PGF2α) analog characterized by the substitution of the C-1 carboxyl group with an N-diethyl amide. Prostaglandin (PG) esters and N-ethyl amides have demonstrated ocular hypotensive properties, with N-ethyl amides introduced as alternative options for PG hypotensive prodrugs. Studies indicate that both bovine and human corneal tissues can convert N-ethyl amides of various PGs into their free acid forms at a rate of approximately 2.5 µg/g corneal tissue/hr. However, dialkyl amides like 17-phenyl trinor PGF2αdiethyl amide resist conversion by corneal amidase, showing no detectable transformation into free acids. This characteristic suggests their potential as valuable investigative tools for assessing the intrinsic intraocular hypotensive activities of PG amides.

N-Cyclohexanecarbonylpentadecylamine (Compound 1), an inhibitor of N-Acylethanolamine hydrolyzing acid amidase (NAAA) with an inhibition concentration (IC50) of 4.5 μM, is utilized in inflammation and pain research [1].