gpx4

GPX4-IN-5 is a small molecule covalent GPX4 inhibitor (IC50: 0.12 μM) with antitumour activity.GPX4-IN-5 induces ferroptosis and can be used for the prevention and treatment of triple-negative breast cancer (TNBC).

GPX4-IN-6 is a small molecule covalent GPX4 inhibitor (IC50: 0.12 μM) with antitumour activity.GPX4-IN-6 induces ferroptosis and is used for the treatment= and prevention of triple negative breast cancer (TNBC).

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.

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.

JKE-1674 is an orally active glutathione peroxidase 4 (GPX4) inhibitor and the active metabolite of ML-210, which is converted to butyronitrile oxide JKE-1777. JKE-1674 kills LOX-IMVI cells in the same manner as ML-210 and is completely rescued by ferroptosis inhibitors.

FIN56 is an iron death-specific inducer that binds to and activates squalene synthase, inducing ferroptosis by triggering GPX4 degradation. FIN56 can be used in studies of ferroptosis regulatory mechanisms, autophagy-ferroptosis crosstalk, and tumor therapy.

BCP-T.A is an ferroptosis inducer that acts by binding to GPX4.

N6F11 is a novel, selective and potent inducer of ferroptosis with anticancer and antitumour activity that promotes GPX4 degradation by binding to TRIM25 in cancer cells.N6F11 can be used to study pancreatic cancer.

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.

PROTACGPX4 degrader-4 is a GPX4 PROTAC degrader with a DC50 of 5.32 nM. It inhibits the activity of cancer cell lines RT4, T24, and J82 with IC50 values of 0.09, 2.97, and 7.58 μM, respectively. This compound elevates lipid ROS levels and induces ferroptosis in T24 and RT4 cells. In T24 tumor-bearing BALB/c nude mouse models, PROTACGPX4 degrader-4 demonstrates antitumor activity. It is applicable to bladder cancer research.

GPX4 9i is a ferroptosis inducer that exhibits cytotoxicity towards HT-1080 cells, with an IC50 of 0.007 µM. This cytotoxic effect can be mitigated by the use of the ferroptosis inhibitor, ferrostatin-1.

PROTACGPX4 degrader-2 (compound 18a) is a proteolysis-targeting chimera (PROTAC) that targets the degradation of glutathione peroxidase 4 (GPX4), with a DC50, 48h value of 1.68 μM. It induces the accumulation of lipid peroxides and mitochondrial depolarization, subsequently triggering ferroptosis. Additionally, PROTACGPX4 degrader-2 exhibits antiproliferative activity.

GPX4/CDK-IN-1 is a dual inhibitor of GPX4 and CDK, exhibiting IC50 values of 542.5 nM for GPX4, 191.2 nM for CDK4, and 68.1 nM for CDK6. [GPX4/CDK-IN-1] demonstrates significant anti-cancer cell growth activity in vivo.

PROTACGPX4 degrader-5 is a potent and highly selective GPX4 PROTAC degrader with a DC50 of 28 nM. It effectively induces ferroptosis with low toxicity to normal cells and significantly increases reactive oxygen species (ROS). PROTACGPX4 degrader-5 exhibits antiproliferative effects against various tumor cells and is commonly used in cancer research.

GPX4 degrader-1 (Compound RS-1) is a GPX4 degrader utilizing hydrophobic tag (HyT) technology, demonstrating a DC50 of 8.9 nM in HT1080 cells. It induces GPX4 degradation, triggers ferroptosis, and increases lipid ROS levels. In a mouse breast cancer model, GPX4 degrader-1 exhibits potent antitumor activity.

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

PROTAC GPX4 Degrader-1 (DC-2) is a PROTAC-based compound that efficiently degrades GPX4, demonstrating a degradation concentration (DC 50) of 0.03 μM in HT1080 cells [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.

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.

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.

GPX4-IN-9 (Compound A16) is an inhibitor of glutathione peroxidase 4 (GPX4) that specifically targets GPX4, both in vitro and in vivo, to induce ferroptosis. It exhibits cytotoxic effects on pancreatic cancer cells and can be utilized for cancer research.

GPX4-IN-19 is a highly effective small-molecule inhibitor of glutathione peroxidase 4 (GPX4) with an IC50 value of 0.311 μM, which exerts its pharmacological activity by covalently binding to the Sec46 active site of GPX4, thereby disrupting lipid peroxide detoxification, inducing intracellular Fe²⁺ accumulation, elevating lipid peroxide (LPO) and reactive oxygen species (ROS) levels, triggering ferroptosis-associated DNA damage, demonstrating strong anti-proliferative effects with high ferroptosis selectivity, and providing a robust experimental tool for mechanistic and therapeutic studies in Triple-Negative Breast Cancer (TNBC).

GPX4-AUTAC is an autophagy-mediated degrader (AUTAC) targeting GPX4. It consists of the inhibitor ML162-yne, a degradation tag FBnG, and a glycol linker. GPX4-AUTAC facilitates the ubiquitination of GPX4 by the E3 ligase TRAF6 and enhances its interaction with GPX4 and p62, leading to selective autophagy-dependent degradation of GPX4. This compound significantly induces ferroptosis and demonstrates potent anticancer activity in breast cancer cells, patient-derived organoids (PDOs), and MDA-MB-231 tumor xenograft mouse models. It shows strong synergy when used in combination with Sulfasalazine (SAS) or chemotherapy drugs (Paclitaxel or Cisplatin).