Glutathione Peroxidase

ML-210??the most potent compound in the nitroisoxazole series?? is a selective covalent inhibitor of glutathione peroxidase 4 (GPX4) by binding the selenocysteine residue.

GPX4-IN-11 is a potent inhibitor of GPX4, demonstrating a KD of 45.7 μM. This compound is significant in the study of ferroptosis, enabling researchers to investigate the mechanisms underlying oxidative stress and cell death. Its utility in various biological assays contributes to the understanding of GPX4's role in disease processes and potential therapeutic approaches.

GPX4-IN-13 is a potent inhibitor of GPX4, targeting its role in cellular antioxidant defense mechanisms. This compound exhibits significant anticancer activity by promoting ferroptosis and reducing proliferation in thyroid cancer cells. It demonstrates inhibitory effects on the growth of various thyroid cancer cell lines, with IC50 values of 8.39 μM for N-thy-ori-3-1, 10.28 μM for MDA-T32, and 8.18 μM for MDA-T41. GPX4-IN-13 is instrumental for research in cancer biology and therapeutic development targeting GPX4-dependent pathways.

GPX4-IN-12 is a non-covalent inhibitor of Glutathione Peroxidase 4 (GPX4), primarily targeting this enzyme to induce ferroptosis. This compound effectively inhibits cell proliferation in HT1080 cells, making it a valuable tool for studying the mechanisms of ferroptosis and its implications in cancer research. GPX4-IN-12 is suitable for investigations into oxidative stress and related pathways within various biological contexts.

GPX4-IN-21 is a selective inhibitor of glutathione peroxidase 4 (GPX4), a key regulator in cellular redox homeostasis. This compound effectively induces ferroptosis by downregulating ferroptosis-related proteins, including SLC7A11, SLC11A2, and GPX4, leading to increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA). GPX4-IN-21 demonstrates significant anti-proliferative activity and is useful for investigating therapeutic strategies in cancer research, particularly in models of melanoma.

NPD4928 is a potent GPX4 inhibitor that enhances RSL3-dependent ferroptosis through its unique mechanism of action. By binding to ferroptosis suppressor protein 1 (FSP1), NPD4928 effectively inhibits its enzymatic activity, thereby promoting ferroptotic cell death. This compound is valuable for research applications focused on studying ferroptosis pathways and identifying potential therapeutic targets in cancer and neurodegenerative diseases.

GPX4-IN-6 is a covalent inhibitor of GPX4, exhibiting an IC50 of 0.13 μM. This compound effectively induces ferroptosis, making it a valuable tool for studying mechanisms related to triple-negative breast cancer (TNBC). Its role in modulating oxidative stress pathways presents significant implications for cancer research and therapeutic development.

JKE-1716 is a potent and selective inhibitor of glutathione peroxidase 4 (GPX4). It induces ferroptosis through the covalent modification of GPX4, making it a valuable tool for studying iron-dependent cell death mechanisms. This compound is applicable in research focusing on cancer biology, neurodegenerative diseases, and oxidative stress-related studies.

RSL3-NH2 is a selective inhibitor of GPX4, a crucial regulator of lipid peroxidation and ferroptosis. By promoting ferroptosis in cancer cells, RSL3-NH2 serves as an effective tool for studying cell death pathways and cancer metabolism. Additionally, this compound can be utilized as a cytotoxic payload in the development of antibody-drug conjugates (ADCs), enhancing targeted therapeutic strategies in cancer research.

GPX4-IN-9 is a selective inhibitor of glutathione peroxidase 4 (GPX4), effectively promoting ferroptosis under both in vitro and in vivo conditions. This compound demonstrates significant cytotoxic effects on pancreatic cancer cells, making it a valuable tool for cancer research. Its mechanisms of action offer insights into the role of GPX4 in cancer cell survival and potential therapeutic strategies targeting ferroptosis.

GPX4-IN-19 is a potent inhibitor of GPX4, exhibiting an IC50 of 0.311 μM through covalent binding to the Sec 46 site. This compound demonstrates significant anti-proliferative effects with a high selectivity for inducing ferroptosis, characterized by intracellular Fe2+ accumulation and elevated levels of lipid peroxides (LPOs) and reactive oxygen species (ROS). GPX4-IN-19 is particularly relevant for research in Triple-Negative Breast Cancer (TNBC), as it induces ferroptosis and subsequent DNA damage.

JKE-1674 is a potent inhibitor of glutathione peroxidase 4 (GPX4), functioning through modulation of cellular redox status. This orally active compound, an analog of ML-210 with a structural modification to the nitroisoxazole ring, demonstrates strong cytotoxicity against LOX-IMVI cells, akin to that of ML-210. Notably, cell viability is restored upon treatment with ferroptosis inhibitors, underscoring its utility in studying ferroptotic cell death pathways and oxidative stress in various biological contexts.

GPX4-IN-3 is a selective inhibitor of glutathione peroxidase 4 (GPX4), serving as a potent inducer of ferroptosis. At a concentration of 1 μM, GPX4-IN-3 demonstrates 71.7% inhibition of GPX4 activity. This compound is valuable for research applications focused on oxidative stress, cell death mechanisms, and potential therapeutic strategies against various cancers and neurodegenerative diseases.

GPX4-IN-5 is a potent covalent inhibitor of GPX4, exhibiting an IC50 of 0.12 μM. This compound induces ferroptosis, demonstrating significant anti-tumor activity. GPX4-IN-5 is particularly relevant for research applications focused on triple-negative breast cancer (TNBC).

4-Aminobenzohydrazide is a potent inhibitor of glutathione peroxidase, demonstrated to induce oxidative stress in neutrophils, with an IC50 value of 43.6 μM for reactive oxygen species (ROS) generation. This compound serves as a valuable tool for investigating oxidative stress-related mechanisms and has applications in subacute stroke research. Its ability to irreversibly inhibit myeloperoxidase further reinforces its utility in studying inflammatory processes and cellular responses.

GPX4-IN-4 is a selective inhibitor of glutathione peroxidase 4 (GPX4). This compound demonstrates significant efficacy in disrupting GPX4 activity, leading to increased oxidative stress and cellular apoptosis. GPX4-IN-4 is particularly relevant for cancer research, as it can help elucidate the role of GPX4 in tumor growth and survival, providing insights for potential therapeutic strategies.

ML162-yne is a selective GPX4-inhibitor affinity probe that utilizes click chemistry for targeted interactions. Featuring an alkyne functional group, this reagent can participate in copper-catalyzed azide-alkyne cycloaddition (CuAAc), enabling efficient conjugation with azide-containing molecules. This capability makes ML162-yne valuable for studying the role of GPX4 in various biological processes and for developing novel therapeutic strategies.

Sorbifolin is a flavone glucoside that functions as a potent inhibitor of glutathione peroxidase. It exhibits myeloperoxidase inhibitory activity with an IC50 value of 19.2 nM, along with significant radical scavenging properties. Due to its ability to modulate oxidative stress-related pathways, Sorbifolin is valuable for research applications focusing on inflammatory diseases and redox homeostasis.

GPX4-IN-15 is a specific inhibitor of GPX4, demonstrating a 19.8% inhibition at a concentration of 1 μM. This compound effectively inhibits the proliferation of various cancer cell lines, including MDA-MB-468, BT-549, and MDA-MB-231, with IC50 values of 0.86 μM, 0.96 μM, and 0.48 μM, respectively. GPX4-IN-15 is a valuable tool for researchers investigating the role of GPX4 in cancer biology and therapeutic resistance.

GPX4-IN-17 is a selective inhibitor of GPX4, demonstrating potent cytotoxicity with an IC50 of 0.3 nM and high binding affinity (KD = 20.4 nM). This compound effectively inhibits tumor growth in xenograft models while exhibiting minimal cytotoxic effects on normal tissues. GPX4-IN-17 is a valuable tool for enhancing cancer chemotherapy and addressing tumor resistance, making it a significant reagent for antitumor research applications.

GPX4-IN-1 is a potent inhibitor of glutathione peroxidase 4 (GPX4), a critical enzyme involved in cellular redox regulation. This compound exhibits significant antiproliferative activity, making it a valuable tool in cancer research. GPX4-IN-1 can be utilized to investigate mechanisms of cancer cell survival and sensitivity to oxidative stress, providing insights into targeted therapies for malignancies.

STIM1-TFR1-IN-1 is an inhibitor of the STIM1-transferrin receptor 1 (TFR1) protein complex, exhibiting a binding affinity (Kd) of 2.18 μM to the STIM1-CD protein. This compound effectively disrupts the STIM1-TFR1 interaction, thereby decreasing TFR1-mediated iron uptake while inhibiting ferroptosis, lipid peroxidation, and reactive oxygen species (ROS) production. STIM1-TFR1-IN-1 also enhances glutathione peroxidase 4 (GPX4) activity and improves the glutathione/oxidized glutathione ratio, promoting neuroprotective effects and mitigating brain injury. This reagent is particularly relevant for studies focusing on intracerebral hemorrhage.

GPX4-IN-8 is a selective inhibitor of Glutathione Peroxidase 4 (GPX4), a key enzyme involved in cellular redox homeostasis. This compound exhibits significant antiproliferative activity, making it a valuable tool for research focusing on oxidative stress, ferroptosis, and cancer biology. GPX4-IN-8 can effectively facilitate investigations into the role of GPX4 in various disease models and therapeutic contexts.

LOC1886 is a covalent inhibitor targeting glutathione peroxidase 4 (GPX4), crucial for regulating oxidative stress within cells. It exhibits robust biological activity that aids in the investigation of ferroptosis and related cell death pathways. This compound is particularly useful for research applications focused on cancer biology, neurodegenerative diseases, and the study of oxidative damage mechanisms.

α-MSH (11-13) acetate is a selective melanocortin-1 receptor ligand that functions as an inhibitor of NF-κB, GPx activity, and HIV replication. It induces an acute elevation of intracellular calcium levels under certain costimulation or pathway inhibition conditions. This compound effectively suppresses TNF-α-induced NF-κB activation, inhibits colony formation of Staphylococcus aureus and Candida albicans, and demonstrates potential in the study of infections related to these pathogens, as well as in traumatic brain injury, corneal epithelial wounds, and inflammatory bowel disease research.

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

AZD-5904 is a potent orally bioavailable MPO inhibitor. In preclinical studies, AZD-5904 inhibited the isolated MPO enzyme with an IC50 of 140 nM and was approximately equipotent in assays of rat and mouse MPO enzyme activity.

Verdiperstat (AZD3241) is a selective, irreversible and orally active myeloperoxidase (MPO) inhibitor, with an IC50 of 630 nM, and can be used in the research of neurodegenerative brain disorders.

ML162 is a covalent glutathione peroxidase 4 (GPX4) inhibitor. ML162 has a selective lethal effect on mutant RAS oncogene-expressing cell lines.

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

4-Methylesculetin is a coumarin derivative that functions as a potent inhibitor of glutathione peroxidase. This compound exhibits significant antioxidant and anti-inflammatory properties, effectively inhibiting myeloperoxidase activity. In research applications, 4-Methylesculetin demonstrates the ability to attenuate bone resorption by downregulating elevated levels of bone-related exoglycosidases, cathepsin D, and tartrate-resistant acid phosphatases. Additionally, it reduces the expression of pro-inflammatory markers such as TNF-α, IL-1β, IL-6, COX-2, and PGE2, making it a valuable tool for studying inflammatory diseases.

Anti-NSCLC agent-2 (compound 6o) functions as a dual inhibitor of SLC7A11 and GPX4, key regulators of ferroptosis. By disrupting redox homeostasis and depleting glutathione levels, this compound facilitates the accumulation of lipid peroxides, leading to the induction of ferroptosis in non-small cell lung cancer (NSCLC) cells. Anti-NSCLC agent-2 is a valuable tool for research focused on understanding and targeting non-small cell lung cancer mechanisms.