aminotransferase

Alanine aminotransferase (ALT), a pyridoxal-dependent enzyme, catalyzes the reversible interconversion of L-alanine and 2-oxoglutarate into pyruvate and L-glutamate [1].

Aspartate aminotransferase (AST) is a transaminase enzyme, is often used in biochemical studies. Aspartate aminotransferase catalyzes aspartate and alpha-ketoglutarate converts to oxaloacetate and glutamate. Aspartate aminotransferase can be found in cerebrospinal fluid, exudates, and transudates [1] .

Levetiracetam (SIB-S1) is a relatively unique anticonvulsant that is typically used in combination with other antiepileptic medications for partial onset seizures. Levetiracetam has been linked to rare instances of serum aminotransferase and alkaline phosphatase elevations during treatment and to rare cases of clinically apparent drug induced liver disease.

7-Methyl-6-mercaptopurine (7-Methyl-6-thiopurine) is an inhibitor of PRPP aminotransferase, inhibits IMP metabolism and prevents purine, DNA and RNA synthesis.

BJJF078, an aminopiperidine derivative, is a potent inhibitor of recombinant human and mouse glutamine aminotransferase (TG2) activity, with IC50 values of 41 and 54 nM for human and mouse glutamine aminotransferase, respectively.BJJF078 inhibits TG1 enzyme, with an IC50 of 0.16 μM.BJJF078 can be used to study multiple sclerosis (MS). BJJF078 can be used to study multiple sclerosis (MS).

ERG240 is an inhibitor of branched-chain amino acid aminotransferase 1 (BCAT1). ERG240 can be used for the research of rheumatoid arthritis, cancer, and bone disease.

Meropenem (SM 7338) is a carbapenem antibiotic with broad spectrum of activity that is administered intravenously and used for severe bacterial infections due to sensitive agents. Meropenem is a common cause of mild transient aminotransferase elevations and can rarely result in clinically apparent, cholestatic liver injury.

Vortioxetine (Lu AA 21004) is a serotonergic antidepressant used for major depression disorders. Vortioxetine has been associated with a low rate of minor serum aminotransferase elevations during treatment.

Nitisinone-13C6is intended for use as an internal standard for the quantification of nitisinone by GC- or LC-MS. Nitisinone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), which converts 4-hydroxyphenylpyruvate (HPPA) to homogentisate in the tyrosine catabolic pathway.1Nitisinone increases urinary levels of HPPA and 4-hydroxyphenyllactate (HPLA) in rats when administered at a dose of 10 mg/kg. Nitisinone (3 mg/kg) prevents the neonatal lethality of fumarylacetoacetate hydrolase (FAH) deficiency in mice when administered to pregnant dams.2It exhibits hepatoprotective effects inFAH-/-mice, such as prevention of increases in plasma levels of aspartate serine aminotransferase (AST) and conjugated bilirubin, when administration is continued following birth at a dose of 1 mg/kg. Nitisinone (100 μg) decreases urinary excretion of homogentisate and increases urinary excretion of HPPA, HPLA, and 4-hydroxyphenylacetate in a mouse model of alkaptonuria induced by ethylnitrosourea.3Formulations containing nitisinone have been used in the treatment of hereditary tyrosinemia type 1 (HT-1). 1.Ellis, M.K., Whitfield, A.C., Gowans, L.A., et al.Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dioneToxicol. Appl. Pharmacol.133(1)12-19(1995) 2.Grompe, M., Lindstedt, S., al-Dhalimy, M., et al.Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type INat. Genet.10(4)453-460(1995) 3.Suzuki, Y., Oda, K., Yoshikawa, Y., et al.A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuriaJ. Hum. Genet.44(2)79-84(1999)

Hydroxypyruvic acid is an intermediate in the metabolism of glycine, serine, and threonine. It is a substrate for serine-pyruvate aminotransferase and glyoxylate reductase/hydroxypyruvate reductase.

5-Fluoromethylornithine (5-FMOrn) dihydrochloride is a specific, irreversible inhibitor of L-ornithine:2-oxoacid aminotransferase (OAT), utilized in research pertaining to gyrate atrophy of the choroid and retina [1] [2].

Milnacipran hydrochloride (Savella) is a serotonin and norepinephrine reuptake inhibitor used to treat major depressive disorders. Milnacipran hydrochloride is an enantiomer of milnacipran, which is used to treat fibromyalgia. Milnacipran hydrochloride and milnacipran have been associated with a low rate of transient elevations in serum aminotransferase levels during treatment and with rare instances of clinically apparent acute liver injury with jaundice.

BFF122 is an inhibitor of kynurenine aminotransferase II (KAT II).

ZLY032 is a dual agonist of free fatty acid receptor 1 (FFAR1/GPR40; EC50= 68 nM in a FLIPR assay) and peroxisome proliferator-activated receptor δ (PPARδ; EC50= 102 nM in a reporter assay).1It is selective for FFAR1 and PPARδ over PPARα and PPARγ (EC50s = >10 μM for both). ZLY032 (40 mg/kg, twice per day) reduces blood glucose levels in an oral glucose tolerance test and decreases plasma total cholesterol and triglyceride levels in theob/obmouse model of metabolic disease.2It reduces hepatic steatosis and plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a methionine and choline-deficient diet at the same dose. 1.Li, Z., Chen, Y., Zhou, Z., et al.Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agentsEur. J. Med. Chem.164352-365(2019) 2.Li, Z., Zhou, Z., Hu, L., et al.ZLY032, the first-in-class dual FFA1/PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosisPharmacol Res.159105035(2020)

GOT1 inhibitor-1 (GOT1 inhibitor 2c) is a novel, potent and non-covalent inhibitor of glutamate oxaloacetate transaminase 1 (GOT1) with an IC50 of 8.2 uM.

L-Canaline, a nonprotein amino acid found in many leguminous plants, exhibits potent anticancer and antiproliferative effects. It effectively inhibits the growth of the malaria parasite Plasmodium falciparum with an IC50 of 297 nM. Additionally, L-Canaline acts as a cytotoxic metabolite produced from L-canavanine through arginase catalysis and serves as a potent and irreversible inhibitor of ornithine aminotransferase.

U-7524, also known as AOAA and Aminooxyacetic acid, is an inhibitor of 4-aminobutyrate aminotransferase (GABA-T). AOAA is also a general inhibitor of pyridoxal phosphate (PLP)-dependent enzymes (this includes GABA-T). It functions as an inhibitor by attac

5-aminovalerate (or 5-aminopentanoic acid) is a lysine degradation product. It can be produced both endogenously or through bacterial catabolism of lysine. 5-aminovalerate is formed via the following multi-step reaction: L-lysine leads to cadverine leads

Mirtazapine (6-Azamianserin) is a tetracyclic antidepressant with a somewhat unique mechanism of action. Mirtazapine therapy can be associated with transient asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury.

Asenapine Maleate (Org 5222 maleate) is a second generation (atypical) antipsychotic agent that is taken sublingually and used in the treatment of schizophrenia and manic or mixed episodes associated with bipolar 1 disorder. Asenapine is associated with a low rate of transient and mild serum aminotransferase elevations during therapy but has not been linked to instances of clinically apparent acute liver injury.

SHS4121705 is an orally bioavailable mitochondrial uncoupler.1It increases oxygen consumption rate in L6 rat myoblast cells with an EC50value of 4.3 μM. SHS4121705 (25 mg/kg per day in the diet) reduces hepatic steatosis, liver triglyceride levels, and plasma alanine aminotransferase (ALT) levels in Stelic animal model (STAM) mice, a model of non-alcoholic steatohepatitis (NASH). 1.Salamoun, J.M., Garcia, C.J., Hargett, S.R., et al.6-Amino[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol derivatives as efficacious mitochondrial uncouplers in STAM mouse model of nonalcoholic steatohepatitisJ. Med. Chem.63(11)6203-6224(2020)

iGOT1-01 is an effective inhibitor of glutamate oxaloacetate transaminase 1(GOT1) . iGOT1-01 has IC50s of 84.6 μM and 11.3 μM in GOT1/MDH1 assay and GOT1/GLOX/HRP assay, respectively. iGOT1-01 can be used in anti-cancer studies.

DapL-IN-1 is a L,L-diaminopimelate aminotransferase (DapL) inhibitor.

Milnacipran-d10 Hydrochloride is a deuterated compound of Milnacipran Hydrochloride. Milnacipran Hydrochloride has a CAS number of 101152-94-7. Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor used to treat major depressive disorders. Levomilnacipran is an enantiomer of milnacipran, which is used to treat fibromyalgia. Levomilnacipran and milnacipran have been associated with a low rate of transient elevations in serum aminotransferase levels during treatment and with rare instances of clinically apparent acute liver injury with jaundice.

L-Cycloserine ((-)-Cycloserine) irreversibly inhibits GABA pyridoxal 5′-phosphate-dependent aminotransferase in E. coli, as well in the brains of various animals, results in increased levels of gamma-aminobutyric acid (GABA), which is an inhibitory neurotransmitter in vivo.

4-Hydroxyphenylpropionylglycine, a metabolite derived from the conditionally essential amino acid tyrosine, is synthesized through a process involving aromatic amino acid aminotransferase and tyrosine aminotransferase activities, with subsequent modifications by gut microbiota and glycine conjugation. Additionally, it serves as a metabolite of the phenol phloretin.

Quinapril hydrochloride (PD-109452-2) is an angiotensin-converting enzyme (ACE) inhibitor used in the therapy of hypertension and congestive heart failure. Quinapril hydrochloride is associated with a low rate of transient serum aminotransferase elevations, but has yet to be linked to instances of acute liver injury.

CPP-115 is a GABA-aminotransferase inhibitor and a high-affinity vigabatrin analogue.

6-azathymine is a potent inhibitors of D-3-aminoisobutyrate-pyruvate aminotransferase. 6-Azauracil acted as a competitive inhibitor with respect to beta-alanine, and was an uncompetitive inhibitor with respect to pyruvic acid with a Ki of approximately 8.9 mM.

Ac-Ala-OH (N-Acetyl-L-alanine) is a substrate for Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit, Myelin basic protein, GTP-binding nuclear protein Ran, Tropomyosin alpha 4 chain, HIV-1 Rev binding protein 2, Xaa-Pro dipeptidase, Thymosin beta-10, Actin-like protein 3, Alanine aminotransferase, Serine/threonine protein Phosphatase PP1-beta catalytic subunit,10 kDa heat shock protein (mitochondrial), Calmodulin and Beta-1-syntrophin.

Meropenem-d6-1 is a deuterated compound of Meropenem-1. Meropenem-1 has a CAS number of 96036-03-2. Meropenem is a carbapenem antibiotic with broad spectrum of activity that is administered intravenously and used for severe bacterial infections due to sensitive agents. Meropenem is a common cause of mild transient aminotransferase elevations and can rarely result in clinically apparent, cholestatic liver injury.

Benazepril-d5 HCl is a deuterated compound of Benazepril HCl. Benazepril HCl has a CAS number of 86541-74-4. Benazepril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the therapy of hypertension. Benazepril is associated with a low rate of transient serum aminotransferase elevations and has been linked to rare instances of acute liver injury.

Pap12-6, an antibacterial peptide originating from the first twelve N-terminal amino acids of papiliocin found in P. xuthus larvae, exhibits activity against a range of eight Gram-negative bacteria (e.g., E. coli, P. aeruginosa, S. syphimurium with MIC50s=4-8 µM) and Gram-positive bacteria (e.g., S. aureus, methicillin-resistant S. aureus 3126, B. subtilis, and S. epidermidis with MIC50s=4-8 µM), without compromising the viability of human erythrocytes, mouse RAW 264.7 macrophages, human HaCaT keratinocytes, or human HEK293 kidney cells at 25 µM. It causes membrane depolarization in E. coli at 4 and 8 µM and, upon preincubation at 10 µM, decreases nitrite (NO2-), Tnf-α, and Il-6 secretion in LPS-stimulated RAW 264.7 macrophages. In a murine model, Pap12-6 enhances survival rates and diminishes colony forming units (CFUs) in several organs upon E. coli infection at 10 mg/kg and 1 mg/kg doses, respectively. Additionally, at a 1 mg/kg dose, it lowers serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels, as well as blood urea nitrogen levels in E. coli-induced sepsis, indicating its therapeutic potential for bacterial infections without affecting host cell viability.

Clonidine (Kapvay) is a centrally active alpha-adrenergic agonist used predominantly as an antihypertensive agent, usually in combination with other agents. Despite wide-scale use for many years, clonidine has not been linked definitively to either serum aminotransferase elevations or clinically apparent liver injury.

Hydroxypyruvic acid lithium hydrate is an intermediate in the metabolism of serine, glycine, and threonine. It is a substrate for serine-pyruvate aminotransferase and glyoxylate reductase/hydroxypyruvate reductase.

4-Hydroxyphenylpyruvic acid is an enzyme inhibitor.4-Hydroxyphenylpyruvic acid (4-HPPA) is a keto acid that is involved in the tyrosine catabolism pathway. It is a product of the enzyme (R)-4-hydroxyphenyllactate dehydrogenase (EC 1.1.1.222) and is formed during tyrosine metabolism. The conversion from tyrosine to 4-HPPA is catalyzed by tyrosine aminotransferase. Additionally, 4-HPPA can be converted to homogentisic acid which is one of the precursors to ochronotic pigment. The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction that converts 4-hydroxyphenylpyruvic acid to homogentisic acid. A deficiency in the catalytic activity of HPD is known to lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been shown that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency . Moreover, 4-hydroxyphenylpyruvic acid is also found to be associated in phenylketonuria, which is also an inborn error of metabolism. There are two isomers of HPPA, specifically 4HPPA and 3HPPA, of which 4HPPA is the most common.

NG,NG-dimethyl-L-arginine-d6 (ADMA-d6) (hydrochloride) is intended for use as an internal standard for the quantification of NG,NG-dimethyl-L-arginine by GC- or LC-MS. ADMA is an endogenous inhibitor of nitric oxide synthase (NOS). It is formed from arginine by protein arginine methyltransferases (PRMTs) and degraded by dimethylarginine dimethylaminohydrolases (DDAHs) and alanine-glyoxylate aminotransferase 2 (AGXT2). ADMA levels are increased concomitant with an increase in blood pressure in Dahl salt-sensitive rats fed a high-salt diet. ADMA levels are increased in the plasma in a variety of endothelial dysfunction-related diseases, including hypertension, congestive heart failure, and end-stage renal disease.

MD001 is a dual agonist of peroxisome proliferator-activated receptor α (PPARα) and PPARγ.1 It binds to PPARα and PPARγ (Kds = 9.55 and 0.14 μM, respectively) but does not bind to PPARβ/δ at concentrations up to 500 μM. It increases transcriptional activity of PPARα and PPARγ in a cell-based luciferase reporter assay when used at a concentration of 10 μM. MD001 (10 μM) increases expression of PPARα, PPARγ, and retinoid X receptor (RXR), as well as PPARα and PPARγ target genes, in HepG2 cells. It increases glucose consumption as well as expression of GLUT2 and GLUT4 in HepG2 and 3T3-L1 cells, respectively, in a concentration-dependent manner. MD001 (20 mg/kg) decreases levels of glucose, insulin, free fatty acids, triglycerides, LDL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in blood and reduces the size and number of hepatic lipid droplets in diabetic db/db mice.References1. Kim, S.-H., Hong, S.H., Park, Y.-J., et al. MD001, a novel peroxisome proliferator-activated receptor α/γ agonist, improves glucose and lipid metabolism. Sci. Rep. 9(1), 1656 (2019). MD001 is a dual agonist of peroxisome proliferator-activated receptor α (PPARα) and PPARγ.1 It binds to PPARα and PPARγ (Kds = 9.55 and 0.14 μM, respectively) but does not bind to PPARβ/δ at concentrations up to 500 μM. It increases transcriptional activity of PPARα and PPARγ in a cell-based luciferase reporter assay when used at a concentration of 10 μM. MD001 (10 μM) increases expression of PPARα, PPARγ, and retinoid X receptor (RXR), as well as PPARα and PPARγ target genes, in HepG2 cells. It increases glucose consumption as well as expression of GLUT2 and GLUT4 in HepG2 and 3T3-L1 cells, respectively, in a concentration-dependent manner. MD001 (20 mg/kg) decreases levels of glucose, insulin, free fatty acids, triglycerides, LDL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in blood and reduces the size and number of hepatic lipid droplets in diabetic db/db mice. References1. Kim, S.-H., Hong, S.H., Park, Y.-J., et al. MD001, a novel peroxisome proliferator-activated receptor α/γ agonist, improves glucose and lipid metabolism. Sci. Rep. 9(1), 1656 (2019).

AG-28262 besylate is a VEGFR-2 Inhibitorwhich may affect alanine aminotransferase gene expression and enzymatic activity in the liver.

p5 Ligand for Dnak and DnaJ is a non-apeptide and correspond to the main binding sites of the 23 residues of the mitochondrial aspartate aminotransferase presequence.P5 ligand is a high affinity ligand for Dnak and DnaJ.

Flibanserin (Girosa) is a serotonergic antidepressant used to treat hypoactive sexual desire disorder. Flibanserin has been associated with a low rate of minor serum aminotransferase elevations during treatment but has not been linked to instances of clinically apparent acute liver injury.

Benazepril hydrochloride (CGS 14824A HCl) is an angiotensin-converting enzyme (ACE) inhibitor widely used in the therapy of hypertension. Benazepril hydrochloride is associated with a low rate of transient serum aminotransferase elevations and has been linked to rare instances of acute liver injury.

3-Methyl-GABA, an anticonvulsant agent [1] [2], acts as a potent activator of GABA aminotransferase, fits the binding pocket of the GABA A receptor (GABAaR), and activates L-glutamic acid decarboxylase (GAD).

BCAT-IN-2 is an orally active and selective inhibitor of mitochondrial branched-chain aminotransferase (BCATm), inhibits BCATm and BCATc, and is used in obesity and dyslipidemia.

Lapatinib ditosylate (Lapatinib tosilate) monohydrate is a tyrosine kinase receptor inhibitor used in the therapy of advanced breast cancer and other solid tumors. Lapatinib ditosylate monohydrate therapy is associated with transient elevations in serum aminotransferase levels and rare instances of clinically apparent acute liver injury.

4-Hydroxy-3-methoxybenzylamine hydrochloride (N-Vanillylamine hydrochloride) is an alkaloid that is an intermediate in the biosynthesis of capsaicin. 4-Hydroxy-3-methoxybenzylamine hydrochloride is produced from vanillin by the enzyme vanillin aminotransferase.

Vortioxetine-d8 2HBr is a deuterated compound of Vortioxetine 2HBr. Vortioxetine 2HBr has a CAS number of 508233-74-7. Vortioxetine is a serotonergic antidepressant used for major depression disorders. Vortioxetine has been associated with a low rate of minor serum aminotransferase elevations during treatment.

Clonidine-d4 Hydrochloride is a deuterated compound of Clonidine Hydrochloride. Clonidine Hydrochloride has a CAS number of 4205-91-8. Clonidine is a centrally active alpha-adrenergic agonist used predominantly as an antihypertensive agent, usually in combination with other agents. Despite wide scale use for many years, clonidine has not been linked definitively to either serum aminotransferase elevations or clinically apparent liver injury.

Vortioxetine-d8 is a deuterated compound of Vortioxetine. Vortioxetine has a CAS number of 508233-74-7. Vortioxetine is a serotonergic antidepressant used for major depression disorders. Vortioxetine has been associated with a low rate of minor serum aminotransferase elevations during treatment.

Eplerenone (CGP 30083) is an aldosterone receptor antagonist and potassium-sparing diuretic used in the therapy of hypertension. Eplerenone therapy has been associated with transient elevations in serum aminotransferase levels, but has yet to be linked to cases of clinically apparent drug induced liver disease.