peroxidase

Peroxidase, found in the roots of horseradish, actively involves in oxidizing reactive oxygen species, innate immunity, hormone biosynthesis, and pathogenesis of several diseases.

Glutathione Peroxidase (GSH-Px; EC 1.11.1.9), a member of the peroxidase family, catalyzes the oxidation of reduced glutathione (GSH) to oxidized glutathione (GSSG) by forming a disulfide bridge, while concurrently reducing hydrogen peroxide or lipid peroxides to water, serving as a potent antioxidant and protecting against oxidative stress [1].

GPX4 24, a derivative of (1S,3R)-RSL3, acts as a potent inhibitor of glutathione peroxidase 4 (GPX4) through covalent binding in a concentration-dependent manner within 4T1 murine mammary carcinoma cells. This compound effectively induces ferroptosis in GPX4-dependent HT-1080 fibrosarcoma cells with an EC50 value of 0.16 µM. Additionally, at a dose of 200 mg/kg, GPX4 24 elevates malondialdehyde (MDA) levels in both kidney and plasma of mice, highlighting its impact on lipid peroxidation.

RSL3 (RSL3 1S) is an inhibitor of GPX4, and inhibits system xc- that blocks GSH synthesis (IC50=100 nM). RSL3 is a VDAC-independent activator of ferroptosis that is selective for tumor cells carrying oncogenic RAS.

JKE-1674 is an inhibitor of glutathione peroxidase 4 (GPX4). JKE-1674 is an active metabolite of the GPX4 inhibitor ML-210.

Ampyrone (4-Aminoantipyrine) is a reagent for glucose determination in the presence of peroxidase and phenol.

3,4-Dimethoxybenzyl alcohol is a secondary metabolite of lignin-degrading fungi and is commonly used as a non-phenolic substrate to measure ligninolytic activity.Veratryl alcohol protects lignin peroxidase (LiP) from inactivation by H2O2 and prevents accumulation of LiP III compounds[3].

L-SelenoMethionine (L-(+)-Selenomethionine) is a naturally occurring amino acid. It promotes cell cycle progression and elevates the expression of the antioxidant enzymes thioredoxin reductase, glutathione reductase.

Propylthiouracil (6-n-Propylthiouracil) is a thyroid peroxidase inhibitor and also a 5' -deiodinase inhibitor.

Nicotinic acid hydrazide (NAH) is a hydrazide derivative of nicotinic acid, a heterocyclic organic compound. It is a peroxidase inhibitor and can form solid metal complexes with strong biological activity.

4-Methylesculetin (Methylesculetin) is one of the coumarin derivatives with great anti-oxidant and anti-inflammatory activities.

InhA-IN-2 directly inhibits InhA and does not require activation by the catalase peroxidase KatG.

Dansylglycine is a fluorescent probe for specific determination of halogenating activity of myeloperoxidase and eosinophil peroxidase[1].

MPO-IN-1 is a powerful and orally bioavailable indole-containing inhibitor that acts irrevocably on myeloperoxidase (MPO). With IC50 values of 2.6 μM and 5.3 μM for MPO and thyroid peroxidase (TPO), respectively, MPO-IN-1 effectively inhibits both enzymes. Furthermore, it exhibits remarkable MPO inhibitory activity in an acute inflammation mouse model.

ML-210 (CID 49766530) is a glutathione peroxidase 4 (GPX4) inhibitor (EC50=30 nM) that is covalent and selective. ML-210 has antitumor activity and induces ferroptosis.

ML162 is an inhibitor of GPX4 that is selectively lethal to mutant RAS oncogene-expressing cell lines (IC50s = 25 and 578 nM for HRASG12V-expressing and wild-type BJ fibroblasts, respectively)

Ebselen (CCG-39161) is a organoselenium compound with anti-inflammatory, anti-oxidant and cytoprotective activity. Ebselen acts as a glutathione peroxidase mimetic and is thereby able to prevent cellular damage induced by reactive oxygen species (ROS). In addition, this agent inhibits the activity of a variety of enzymes including nitric oxide synthase (NOS), 5-lipoxygenase, cyclooxygenase, protein kinase C (PKC), NADPH oxidase and gastric H+/K+-ATPase. Furthermore, ebselen may be neuroprotective due to its ability to neutralize free radicals upon NMDA receptor activation thus, reducing lipoperoxidation mediated by glutamate-induced excitotoxicity.

Elamipretide TFA (RX-31 TFA) is a cardiolipin peroxidase inhibitor and mitochondria-targeting peptide[1].

MPO-IN-28 is a novel potent, irreversible Myeloperoxidase (MPO) inhibitor with IC50 of 44 nM.

PF-06282999, a potent and selective myeloperoxidase inhibitor, is potentially useful for the treatment of cardiovascular diseases.

NBDHEX is a potent inhibitor of glutathione S-transferase P1-1 (GSTP1-1) .

2-Pyridinecarbohydrazide (2-Picolinyl hydrazide) is an effective inhibitor of Catalase-peroxidase-NAPDH.

AZD5904 is a potent and irreversible human Myeloperoxidase (MPO) inhibitor(IC50 of 140 nM and has similar potency in mouse and rat).

Tinoridine hydrochloride (Y-3642 hydrochloride) is a non-steroidal anti-inflammatory drug. Tinoridine hydrochloride (5-100 μM), produced a concentration-dependent inhibition on the simultaneous increases in lipid peroxide formation and renin release induced by 50 μM ascorbic acid in the renin granule fraction. On the other hand, indomethacin, hydrocortisone, and prednisolone, which had no ability to inhibit the lipid peroxidation in the renin granule fraction, did not influence the release of renin from the granules. These results suggest that tinoridine suppresses renin release by inhibiting the oxidative disintegration of membranes of renin granules.

RC363 is an inhibitor of ferroptosis and a derivative of the antioxidant and hypocholesterolemic agent probucol .1It reduces 2,2-diphenyl-1-picrylhydrazyl radicals by approximately 40% in a cell-free assay when used at a concentration of 25 μM. RC363 prevents glutamate-induced toxicity in HT22 cultured hippocampal cells (IC50= 234.5 nM) but does not reduce oxidant levels in these cells. It increases the levels of glutathione peroxidase 1 (GPX1) and the activity of GPX in glutamate-challenged HT22 cells when used at a concentration of 3 μM. RC363 inhibits ferroptosis induced by the GPX4 inhibitor RSL3 in HT22 cells (IC50= 173.6 nM). 1.Bueno, D.C., Canto, R.F.S., de Souza, V., et al.New probucol analogues inhibit ferroptosis, improve mitochondrial parameters, and induce glutathione peroxidase in HT22 cellsMol. Neurobiol.57(8)3273-3290(2020)

(E)-2-(2-Chlorostyryl)-3,5,6-trimethylpyrazine (CSTMP) is a stilbene derivative with antioxidant and anticancer activities. It stimulates proliferation of hydrogen peroxide-damaged ECV-304 cells (EC50 = 24.9 nM). CSTMP reduces hydrogen peroxide-induced release of lactate dehydrogenase (LDH) in and increases viability of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner via inhibition of apoptosis. It reverses hydrogen peroxide-induced release of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities as well as increases constitutive nitric oxide synthase (cNOS) activity and nitric oxide (NO) production in HUVECs. CSTMP also induces cell death of A549 non-small cell lung cancer (NSCLC) cells in an IRE1α-dependent manner through induction of IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum (ER) stress and mitochondrial apoptosis.

4-Hydroxyphenylbutazone, a metabolite of Phenylbutazone, functions as an effective reducing cofactor for the peroxidase activity of prostaglandin H synthase (PHS). Phenylbutazone is a nonsteroidal anti-inflammatory drug (NSAID) known for its efficiency in this role.

Verdiperstat (AZD 3241) is a selective, irreversible and orally active myeloperoxidase inhibitor, with an IC50 of 630 nM, and can be used in the research of neurodegenerative brain disorders.

3-Amino-1,2,4-triazole (Trapidil impurity B) is an inhibitor of catalase, capable of inducing the compensatory mechanism for hydrogen peroxide detoxification. This mechanism involves increasing the activities of glutathione peroxidase and glutathione reductase.

3-Bromotyrosine, a product of protein oxidation, is generated after eosinophil activation during allergic responses. It serves as a biomarker for eosinophil peroxidase-induced protein oxidation both in vitro and in vivo. Beyond its association with eosinophils, 3-bromotyrosine levels are significantly elevated in peritoneal exudate from K. pneumoniae-infected mice, indicating a fivefold increase compared to uninfected controls, which implies that neutrophils may release increased levels of oxidized products during inflammation. Furthermore, in humans, allergen-challenged lung samples from patients with allergen-induced asthma show a tenfold increase in 3-bromotyrosine, highlighting its potential as a marker for oxidative stress in allergic conditions.

4-(Imidazol-1-yl)phenol is a potent signal enhancer in horseradish peroxidase (HRP)–luminol chemiluminescence (CL) immunoassays [1].

Coniferin (Abietin) has ATP-dependent transport activity and has anti-oxidation effects. Coniferin has preferred substrates for the coniferin beta-glucosidase, the chromogenic coniferin analogue show the exclusive presence of beta-glucosidase activity in the differentiating xylem, similar to peroxidase activity.

Prostaglandin G2 (PGG2) serves as the initial stable intermediate in the COX pathway, identifiable and characterizable due to its stability. This compound is identified as the C-15 hydroperoxide derivative of PGH2. Typically, PGG2 undergoes rapid metabolism via the inherent peroxidase activity of both COX-1 and COX-2 enzymes, resulting in the production of PGH2. PGH2 is crucial as it is the primary precursor for the generation of 2-series prostaglandins and thromboxanes.

GPX4-IN-3 (26a) is a potent inhibitor of glutathione peroxidase 4 (GPX4), selectively inducing ferroptosis, with a 71.7% inhibition rate at a concentration of 1 μM [1].

Gamma-glutamylcysteine (TFA) ((γ-glutamylcysteine (TFA)), a crucial dipeptide in glutathione (GSH) synthesis and a vital cofactor for the enzyme glutathione peroxidase (GPx), significantly modulates inflammatory responses. It enhances the level of the anti-inflammatory cytokine IL-10, diminishes the concentrations of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and mitigates alterations in metalloproteinase activity in oligomeric Aβ40-treated astrocytes.

Cyanine 5 Tyramide (Tyramide-Cy5) methyl indole, a red fluorescent dye, is utilized as a reporter fluorescent substrate for horseradish peroxidase (HRP)-catalyzed deposition, aiding signal amplification in immunoassays and in situ hybridization of nucleic acids [1]. Store with protection from light.

TMV-IN-4 (Compound 3), a tobacco mosaic virus (TMV) inhibitor, effectively strengthens plant resistance and tolerance to TMV by binding with the TMV helicase. Furthermore, it boosts activities of peroxidase and superoxide dismutase, augmenting tobacco's resilience to TMV infection [1].

Alkyne tyramide is a clickable ascorbate peroxidase 2 (APEX2) probe which enable biotin-independent detection of labeled proteins.

(±)-Licarin A ((±)-trans-Dehydrodiisoeugenol), a dihydrobenzofuran neolignan formed via oxidative coupling of isoeugenol with horseradish peroxidase (HRP) enzyme, exhibits 100% parasite mortality at 200 μM.

4-POBN (Myeloperoxidase Inhibitor 1) is a potent and irreversible inhibitor of myeloperoxidase (IC50 = 0.3 µM). 4-POBN can be used in studies about subacute stroke.

Spirotetramat is an insecticide that demonstrates efficacy against C. pyrinymphs in vitro (LC50= 6.51-12.53 mg AI/L) and achieves a 99.2% mortality rate in C. pyrinymphs within European pear (P. communis) fields 15 days post-application at a dosage of 27 g/hectare. Additionally, it reduces embryonic viability and nymph survival in O. insidiosus. Spirotetramat exhibits aquatic toxicity by altering protein levels in organisms, specifically by increasing glutathione peroxidase (GPX) and superoxide dismutase (SOD) levels, decreasing malondialdehyde (MDA) levels, and causing lethality in Chinese toad (B. gargarizans) tadpoles (LC50= 6.98 mg/L). Its formulations are utilized in agricultural insect control. Spirotetramat is marketed exclusively for research and analytical applications, formulated for controlled laboratory settings without the availability of bulk sizes.

4-AMinoantipyrine-d3 is a deuterated compound of 4-AMinoantipyrine. 4-AMinoantipyrine has a CAS number of 83-07-8. 4-Aminoantipyrine is a reagent for glucose determination in the presence of peroxidase and phenol.

RC574 is an inhibitor of ferroptosis and a derivative of the antioxidant and hypocholesterolemic agent probucol .1It inhibits glutamate-induced cell death in HT22 cells (IC50= 276.2 nM) and mouse primary cortical neurons when used at a concentration of 3 μM. RC574 (3 μM) increases glutathione peroxidase 1 (GPX1) levels and GPX activity, as well as inhibits glutamate-induced mitochondrial superoxide anion production, in HT22 cells. It completely inhibits ferroptosis induced by the GPX4 inhibitor RSL3 in HT22 cells when used at concentrations ranging from 62.5 to 1,000 nM. 1.Bueno, D.C., Canto, R.F.S., de Souza, V., et al.New probucol analogues inhibit ferroptosis, improve mitochondrial parameters, and induce glutathione peroxidase in HT22 cellsMol. Neurobiol.57(8)3273-3290(2020)

MPO-IN-3, a powerful inhibitor of myeloperoxidase (MPO), is described as such in example 191 of WO2013068875A1. MPO, a heme-containing enzyme, is classified under the peroxidase superfamily.

Phenylbutazone-d9 is intended for use as an internal standard for the quantification of phenylbutazone by GC- or LC-MS. Phenylbutazone is a non-steroidal anti-inflammatory drug and an inhibitor of the peroxidase activity of COX (IC50 = ~100 µM in the presence of hydrogen peroxide). It also inhibits prostaglandin I synthase (IC50 = ~25 µM in the presence of hydrogen peroxide). Phenylbutazone (2 mg/kg) reduces increases in type II collagen levels in the inflamed joints of an equine model of LPS-induced acute synovitis. Formulations containing phenylbutazone have been used in the treatment of lameness in horses.

1-Methoxynaphthalene is employed as a substrate for scrutinizing the enzymatic activity of cytochrome c peroxidase (CcP). Additionally, 1-Methoxynaphthalene can serve as a precursor for the synthesis of prenyl naphthalen-ols.

PKUMDL-LC-101-D04 is a potent allosteric activator of glutathione peroxidase 4 (GPX4), a regulator of ferroptosis. GPX4 activity was increased to 150% of control levels when used at a concentration of 20 μM in a cell-free assay, and at a concentration of 61 μM in wild-type, but not Gpx4-/-, mouse embryonic fibroblast (MEF) extracts.PKUMDL-LC-101-D04 (200 μM) reduced cholesterol peroxide-induced MEF death.

MPO-IN-4 (compound 12) is a potent and selective myeloperoxidase (MPO) inhibitor with an IC50 of 25 nM and also demonstrates inhibition of thyroid peroxidase (TPO) with an IC50 of 2.2 μM. MPO-IN-4 has no effect on methyl guanine methyl transferase (MGMT) [1].

PPHP is a substrate utilized for measuring peroxidase enzymes and has been employed to quantify the peroxidase activity of COX-1 and COX-2.

Goitrin ((S)-Goitrin), formed through glucosinolate-myrosinase reactions, serves as a potent inhibitor of thyroid peroxidase, thereby hindering the thyroid's utilization of iodine. Additionally, it demonstrates anti-influenza virus (H1N1) activity.