GPX4 Activator

GCN2iB is an ATP-competitive, selective GCN2 inhibitor with an IC₅₀ of 2.4 nM. GCN2iB inhibits the activation of the GCN2 pathway and upregulates GPX4. GCN2iB enhances the anticancer effect of ASNase against acute lymphoblastic leukemia. GCN2iB increases left ventricular ejection fraction, while reducing fasting blood glucose and myocardial fibrosis. GCN2iB can be used in research related to acute lymphoblastic leukemia, acute myeloid leukemia and diabetic cardiomyopathy.

Gingerenone A is an Nrf2-Gpx4 activator that can induce Ferroptosis in liver damage with oral activity. Gingerenone A has anti-inflammatory, anti-diabetic, anti-tumor, and pro-aging effects in mice.

3-Hydroxyphenylacetic acid is an orally active flavonoid metabolite produced by intestinal flora, with blood pressure-lowering activity. 3-Hydroxyphenylacetic acid can also inhibit ferroptosis by upregulating the expression of GPX4, thereby improving spermatogenic dysfunction in aged mice. In addition, abnormal levels of 3-Hydroxyphenylacetic acid are closely related to certain diseases, such as autism spectrum disorders.

gp91 ds-tat, a biological active peptide, is a NADPH oxidase 2 (Nox2) inhibitor. gp91 ds-tat blocks NADPH oxidase-dependent superoxide production. gp91 ds-tat ameliorates high glucose-induced increase in total ROS, LPOs and iron levels. gp91 ds-tat inhibits homocysteine (Hcy)-induced activation of NLRP3 inflammasomes and restores Hcy-inhibited lysosomal TRPML1 channel activity. gp91 ds-tat improves cerebrovascular and cognitive function in APP/PS1 mice. gp91 ds-tat can be used for the study of Alzheimer’s disease (AD), glomerular inflammation and cardiovascular disease.

PKUMDL-LC-101-D04 (GPX4-Activator-1d4) is a glutathione peroxidase 4 (GPX4) allosteric activator (pEC₅₀=4.7). PKUMDL-LC-101-D04 can inhibit ferroptosis and inflammation.

IRF1-IN-2 (Compound I-19) is an IRF1 inhibitor. IRF1-IN-2 decreases the recruitment of IRF1 to the promoter of CASP1. IRF1-IN-2 inhibits cell death signaling pathway (i.e., cleavage of Caspase 1, GSDMD, IL-1 and PARP1; inhibits the Pho of TKB1, upregulates GPX4 and downregulates FACL4). IRF1-IN-2 has a protective effect on ionizing radiation-induced inflammatory skin injury.

GPX4 activator 2 is a GPX4 activator with a K_a value of 0.426 μM for human GPX4. GPX4 activator 2 reduces lipid hydroperoxide levels, prevents lipid peroxide accumulation, and inhibits ferroptosis. GPX4 activator 2 rescues cell death induced by Erastin (HY-15763). GPX4 activator 2 exerts cardioprotective effects in a mouse model of doxorubicin (HY-15142A)-induced myocardial injury.

Ethylene glycol dimethacrylate is a diester formed by the condensation of Ethylene glycol (HY-Y0338) and Methacrylic acid. Ethylene glycol dimethacrylate is a cross-linking agent for polymers. Ethylene glycol dimethacrylate increases Apoptosis, GPx4, SOD2, ROS. Ethylene glycol dimethacrylate is cytotoxic and genotoxic. Ethylene glycol dimethacrylate exhibits cross-linking activity, enhancing the mechanical properties and stability of materials.

2-Acetamidophenol (Orthocetamol) is a regulator that targets ferroptosis and glutathione metabolic pathways, is the ortho-regioisomer of Paracetamol (HY-66005). 2-Acetamidophenol has anti-atherosclerotic activity, and inhibiting total cholesterol (TC) and triglyceride (TG) in a zebrafish hyperlipidemia model with IC₅₀s for 30 μM and 40 μM, respectively. 2-Acetamidophenol upregulates the expression of glutathione synthesis-related genes (such as GCLC, GCLM, GSS) and iron ion transport genes (such as FPN1, FTH), reduces the accumulation of intracellular reactive oxygen species (ROS) and ferrous ions (Fe²⁺), and enhances the activity of glutathione peroxidase GPX4, thereby inhibiting macrophage phagocytosis of oxidized low-density lipoprotein (ox-LDL) and foam cell formation.

GPX4 activator 1 is an allosteric activator of glutathione peroxidase 4 (GPX4) with a K_d value of 5.86 μM. GPX4 activator 1 binds to a specific region of GPX4 to alter protein binding kinetics and counteract ferroptosis (EC₅₀ = 19.19 μM). GPX4 activator 1 inhibits lipid peroxidation, rescues ferroptotic cell death and maintains cell viability. GPX4 activator 1 can be used in studies related to Doxorubicin (HY-15142A)-induced myocardial injury.

Dexpramipexole ((R)-Pramipexole) is an orally active, blood-brain barrier permeable mitochondrial protective agent. Dexpramipexole upregulates the expression of Parkin, PINK1, GPX4 and FSP1; binds to mitochondrial F1/Fo-ATP synthase; blocks the Na_v1.8 sodium channel; and inhibits the activation of the NLRP3 inflammasome. Dexpramipexole induces mitophagy, inhibits ferroptosis, pyroptosis, apoptosis, neuroinflammation and eosinophilopoiesis; maintains mitochondrial function and redox homeostasis; reduces reactive oxygen species production; and decreases myocardial infarct size. Dexpramipexole is applicable to studies on eosinophilic asthma, myocardial ischemia/reperfusion injury, sepsis-associated encephalopathy, analgesia, and more.

SZ0232 is a selective mPGES-2 inhibitor. SZ0232 binds to the active site of mPGES-2 via hydrogen bonds and π-π stacking, reduces the production of prostaglandin E₂ (PGE₂) and blocks the PGE₂-EP3 pathway. SZ0232 regulates Ferroptosis by activating the heme-dependent p53/SLC7A11/GPX4 axis, inhibits lipid peroxidation, and protects renal tubules. SZ0232 enhances glucose-stimulated insulin secretion, inhibits β-cell senescence, and improves glucose homeostasis. SZ0232 reduces renal lipid accumulation, alleviates fibrosis, and ameliorates renal dysfunction in diabetic mice. SZ0232 inhibits renal cyst growth in polycystic kidney disease models. SZ0232 exhibits an insulinotropic effect that strengthens with the increase of animal age. SZ0232 can be used in studies related to type 2 diabetes, acute kidney injury, diabetic kidney disease, and autosomal dominant polycystic kidney disease.

Picein is an antioxidant and anti-inflammatory agent. Picein can be isolated from the leaves of Picrorhiza kurroa. Picein reduces MDA levels and increases the levels of SOD, GPX and TAC. Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defects by inhibiting Ferroptosis (via activation of the Nrf2/HO-1/GPX4 pathway). Picein prevents scopolamine (HY-N0296)-induced passive avoidance memory impairment in rats. Picein can be used in research related to osteoporotic bone defects and Alzheimer's disease.

DSPE-PEG2000-WLSEAGPVVTVRALRGTGSW is a polypeptide targeting tenascin-X (Tenascin-X) that can be conjugated with liposomes and exosomes. DSPE-PEG2000-WLSEAGPVVTVRALRGTGSW specifically binds to Tenascin-X on the surface of cardiomyocytes, mediates receptor-dependent uptake of nanocarriers, enhances targeted drug delivery of cargo to cardiomyocytes, and increases drug accumulation in cardiac tissue. DSPE-PEG2000-WLSEAGPVVTVRALRGTGSW protects cardiomyocytes treated with LPS, alleviates oxidative stress, repairs mitochondrial function, inhibits ferroptosis and apoptosis, and downregulates the secretion of pro-inflammatory cytokines at the same time. DSPE-PEG2000-WLSEAGPVVTVRALRGTGSW improves cardiac injury and pathological morphology in mice with sepsis-induced cardiomyopathy, restores GPX4 expression, and promotes the internalization of cardiomyocyte-derived exosomes, making it suitable for related research on sepsis-induced cardiomyopathy, myocardial ischemia-reperfusion injury, and other conditions.

Ferroptosis-IN-18 (51), a promethazine derivative, shows strong anti-ferroptosis and anti-oxidant properties. Ferroptosis-IN-18 (51) can be used in the research for intracerebral hemorrhage (ICH).

Ferroptosis-IN-17 (Compound 18) is a ferroptosis (Ferroptosis) inhibitor with an EC₅₀ value of 0.57 μM. Ferroptosis-IN-17 reduces intracellular ferrous ion accumulation, lipid peroxidation, and effectively restores the levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4). Ferroptosis-IN-17 shows good solubility and significant metabolic stability in rat plasma. Ferroptosis-IN-17 is promising for research in tumor suppression, neurodegenerative diseases, and cardiovascular diseases.

GCN2iB acetate is an ATP-competitive, selective GCN2 inhibitor with an IC₅₀ of 2.4 nM. GCN2iB acetate inhibits the activation of the GCN2 pathway and upregulates GPX4. GCN2iB acetate enhances the anticancer effect of ASNase against acute lymphoblastic leukemia. GCN2iB acetate increases left ventricular ejection fraction, while reducing fasting blood glucose and myocardial fibrosis. GCN2iB acetate can be used in research related to acute lymphoblastic leukemia, acute myeloid leukemia and diabetic cardiomyopathy.

DEL-I25 is a potent GPX4 activator. DEL-I25 protects cells from ferroptosis.

2-(3-Hydroxyphenyl-2,4,6-d₃)acetic-2,2-d₂ acid is the deuterium labeled 3-Hydroxyphenylacetic acid (HY-W001083). 3-Hydroxyphenylacetic acid is an orally active flavonoid metabolite produced by intestinal flora, with blood pressure-lowering activity. 3-Hydroxyphenylacetic acid can also inhibit ferroptosis by upregulating the expression of GPX4, thereby improving spermatogenic dysfunction in aged mice. In addition, abnormal levels of 3-Hydroxyphenylacetic acid are closely related to certain diseases, such as autism spectrum disorders.

S27-1047 is a brain-penetrant, potent and selective BChE (eqBChE IC₅₀ = 7.16 nM; hBChE IC₅₀ = 296.10 nM) inhibitor and Nrf2 activator. S27-1047 can directly bind Keap1, disrupt Keap1-Nrf2 interaction (FP IC₅₀ = 36.87 nM), enhance antioxidant enzyme expression and activate the GSH-GPX4 axis to inhibit Aβ-induced ferroptosis. S27-1047 can protect against oxidative stress and neuroinflammation. S27-1047 can be used in Alzheimer's disease research.