Glutathione Peroxidase

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.

ML162 is a covalent glutathione peroxidase 4 (GPX4) inhibitor that induces ferroptosis. ML162 has antitumor activity and selectively inhibits cell lines expressing mutant RAS oncogenes.

Mitiperstat is a potent myeloperoxidase (MPO) inhibitor that is effective in preventing cardiovascular diseases such as heart failure and coronary artery disease.

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.

5-Aminosalicylic Acid (5-ASA) is an anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE.

N-Acetyl lysyltyrosylcysteine amide is a non-toxic, potent, reversible, and specific myeloperoxidase (MPO) tripeptide inhibitor that effectively inhibits MPO production in vivo, attenuates neuronal damage, preserves brain tissue and neurological function post-stroke, and inhibits MPO-dependent hypochlorite (HOCl) production, protein nitration, and LDL oxidation. It is also used in the study of bronchial dysplasia.

Melatonin (Melatonine) is a natural hormone secreted by the pineal gland that activates melatonin receptors. Melatonin is a hormone that regulates the biological clock and also has antioxidant and anti-inflammatory activities.

AZD8309 is a potent, orally available antagonist of the chemokine receptor CXCR2 that regulates neutrophil transport, significantly reduces MPO in the pancreas and lung, and decreases trypsin and elastase activity in the pancreas.AZD8309 can be used to study a range of inflammatory diseases.

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.

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

GSTO1-IN-1 is a potent glutathione S-transferase omega 1 inhibitor (GSTO1) with an IC50 of 31 nM.

PF-1355 (PF 06281355) is a selective 2-thiouracil mechanism-based MPO inhibitor. PF-1355 is used for treatment of vasculitic diseases.

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

TLK117 is an inhibitor of GSTs that reduces the severity of pulmonary fibrosis and can be used to study idiopathic pulmonary fibrosis.

Ezatiostat (TER199(free base)) is a tripeptide analog of glutathione that can selectively inhibit GSTP1-1 catalytic activity.

LAS17 is a selective and highly effective inhibitor of glutathione S-transferase Pi (GSTP1), which inhibits GSTP1 activity in vitro in a concentration-dependent manner. LAS17 has anti-tumor activity and inhibits breast cancer cell growth.

Nabumetone (BRL14777)(BRL14777) is a non-steroidal anti-inflammatory drug and its active metabolite 6MNA inhibits the enzymes cyclo-oxygenase I and II.

Cefdinir (FK-482) is a third-generation, semi-synthetic cephalosporin antibiotic effective against common bacterial infections of the ear, sinus, throat, and skin.

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.

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

4-Aminosalicylic acid (para-aminosalicylic acid) is an analog of para-aminobenzoic acid (PABA) with antitubercular activity.

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.

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

MPO-IN-1 is an orally active myeloperoxidase (MPO) inhibitor, inhibiting MPO and thyroid peroxidase (TPO). It is useful in inflammation research.

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

Ezatiostat hydrochloride (TLK199 HCl) is an effective inhibitor of glutathione S-transferase. Ezatiostat hydrochloride is a novel glutathione analog and the potential treatment of cytopenias. In addition, Ezatiostat hydrochloride has been revealed to selectively bind to and thus inhibit GSTP1-1.

N-Acetyl lysyltyrosylcysteine amide acetate is an effective and selective tripeptide inhibitor of myeloperoxidase (MPO). N-Acetyl lysyltyrosylcysteine amide acetate inhibits MPO-dependent hypochlorous acid (HOCl) generation, protein nitration, and LDL ox

GDCNF-11, an HSP90-based HIM-PROTACGPX4 degrader, facilitates the ubiquitination and degradation of GPX4 through the HSP90 chaperone complex. This reduction in endogenous GPX4 induces ferroptosis in HT-1080 cells, with a DC50 value of 0.08 μM.

GPX4-IN-4 (Compound 24) is a potent inhibitor of GPX4, employed in cancer research [1].

GPX4-IN-16 ((R)-9i) is a potent inhibitor of GPX4 with a KD value of 20.4 nM, exhibiting cytotoxic properties and anticancer activity.

SelB-1 acts as a dual inhibitor of Topoisomerase I II (TopoisomeraseI II), exhibiting anticancer activity suitable for research on prostate and colon cancers. Additionally, SelB-1 can induce the expression of autophagy (autophagy) genes and lipid peroxidation while reducing GSH levels.

GPX4-IN-14 (compound 2c) acts as a GPX4 inhibitor, exhibiting both free radical scavenging activity (with a maximum scavenging rate of 72.52%) and anti-tumor proliferation activity in vitro. This compound targets GPX4 protein, elevating lipid peroxide and intracellular Reactive Oxygen Species (ROS) levels, which induces ferroptosis and contributes to its anti-tumor proliferation effects.

NC-R17, an RSL3-based noncovalent GPX4 degrader implicated in ferroptosis, demonstrates anti-tumor activity and is utilized in the design of noncovalent GPX4-targeted proteolysis targeting chimeras (PROTACs) [1].

Monoamine OxidaseB inhibitor 6 (Compound BT5) is a highly selective, reversible, and competitive MAO-B inhibitor capable of crossing the blood-brain barrier, with an IC50 of 0.11 μM. It exhibits antioxidant and neuroprotective properties, making it suitable for research into neurodegenerative diseases.

GPX4-IN-13 (compound 16), a GPX4 inhibitor, exhibits anticancer properties by diminishing the expression of GPX4, thereby reducing thyroid cell proliferation and inducing ferroptosis. Additionally, this compound effectively inhibits the growth of three distinct thyroid cancer cell lines: N-thy-ori-3-1 (IC 50 =8.39 μM), MDA-T32 (IC 50 =10.28 μM), and MDA-T41 (IC 50 =8.18 μM).

Moracin N, a ferroptosis inhibitor derived from mulberry leaves, exhibits neuroprotective activity by mitigating oxidative stress [1].

ZX782 acts as a GPX4 protein degrader and an inducer of ferroptosis (Ferroptosis), targeting GPX4 for destruction via both the ubiquitin-proteasome system and the autophagy-lysosome pathway. Following the degradation of GPX4 induced by ZX782, there is a significant increase in the accumulation of lipid reactive oxygen species (ROS) in HT1080 cells.

GPX4-IN-15 (Compound C1) is an inhibitor of GPX4, demonstrating an inhibition rate of 19.8% at a concentration of 1 μM. This compound effectively inhibits the proliferation of cancer cell lines MDA-MB-468, BT-549, and MDA-MB-231, with IC50 values of 0.86 μM, 0.96 μM, and 0.48 μM respectively.

LOC1886 is a covalent inhibitor of GPX4, with slightly lower potency compared to RSL3 and ML162.

Ferroptosis-IN-17 (Compound 18) is an inhibitor of ferroptosis with an EC50 value of 0.57 μM. It effectively reduces the accumulation of intracellular ferrous ions and lipid peroxidation while restoring levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4). In rat plasma, Ferroptosis-IN-17 demonstrates good solubility and notable metabolic stability. This compound holds potential for research in tumor suppression, neurodegenerative diseases, and cardiovascular disorders.

GPX4 Activator 2 (Compound C3) serves as an activator of GPX4 and exhibits cardioprotective effects by inhibiting cellular iron death (ferroptosis) with an efficacy concentration (EC50) of 7.8 μM. It is used in the study of myocardial damage.

Lepadin E, a notably cytotoxic compound, effectively stimulates ferroptosis via the canonical p53-SLC7A11-GPX4 pathway. By elevating p53 and repressing SLC7A11 and GPX4 expression, it heightens ROS and lipid peroxidation while also augmenting ACSL4 expression, culminating in cell death. This compound exhibits a considerable antitumor effect [1].

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].