GPX4 Inhibitor

RSL3 ((1S,3R)-RSL3) is an inhibitor of glutathione peroxidase 4 (GPX4) (ferroptosis activator), reduces the expression of GPX4 protein, and induces ferroptotic death of head and neck cancer cell. RSL3 increases the expression of p62 and Nrf2 and inactivates Keap1 in HN3-rslR cells.

ML-210 is a selective and covalent glutathione peroxidase 4 (GPX4) inhibitor with an EC₅₀ of 30 nM. ML-210 binds the GPX4 selenocysteine residue. ML-210 has anti-cancer activity.

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

Pipecolic acid is an orally bioavailable, blood-brain barrier-permeable metabolite of lysine with antioxidant, inhibitor, and inducer activity. Pipecolic acid modulates the YAP-GPX4 signaling pathway, reduces retinal vascular tube formation, and mitigates ferroptosis. Pipecolic acid potentiates voltage-sensitive Ca²⁺ channel currents and induces neuronal apoptosis. Pipecolic acid can be used for the research of diabetic retinopathy.

Cephaeline ((-)-Cephaeline; NSC 32944) is a ferroptosis inducer, with broad-spectrum anticancer and antiviral activities. Cephaeline induces ferroptosis (Ferroptosis) by upregulating p53, inhibiting NRF2, activating ULK3, downregulating the expressions of SLC7A11 and GPX4 in a p53-dependent manner, reducing GSH and mitochondrial membrane potential, and increasing lipid peroxidation and iron accumulation. Cephaeline inhibits cancer cell proliferation, migration and tumor growth. Cephaeline inhibits Ebola virus (EBOV) VLP entry and infection, with IC₅₀ values of 3.27 μM and 22.18 μM respectively; it also inhibits Zika virus (ZIKV) NS5 RdRp activity (IC₅₀ = 976 nM), and binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp and N protein, with K_d values of 8.9 μM and 53.8 μM respectively. Cephaeline can be used in studies related to breast cancer, lung cancer, COVID-19, EBOV and ZIKV infections.

AD-5584 is a selective and blood-brain barrier-penetrant ACSS2 inhibitor (IC₅₀ = 0.86 μM). AD-5584 binds to the nucleotide-binding pocket of ACSS2, blocking CoA binding and acetyl transfer through steric hindrance, thereby inhibiting the conversion of acetate to acetyl-CoA. AD-5584 decreases acetyl-CoA levels, lipid droplet content, FASN expression, E2F1, SLC7A11, and GPX4 levels, and reduces E2F1 occupancy at the SLC7A11 promoter. AD-5584 induces ferroptosis, lipid peroxidation, malondialdehyde accumulation, and cell death, and decreases clonogenic survival and proliferative capacity. AD-5584 can be used for research on breast cancer brain metastasis.

JKE-1674 is an orally active glutathione peroxidase 4 (GPX4) inhibitor and an active metabolite of GPX4 inhibitor ML-210. JKE-1674, an analog of ML-210 in which the nitroisoxazole ring is replaced with an α-nitroketoxime. JKE-1674 can convert into a nitrile oxide JKE-1777. JKE-1674 kills LOX-IMVI cells in a manner that is equipotent to ML-210 and is completely rescued by ferroptosis inhibitors.

GPX4-IN-3 (26a) is a potent glutathione peroxidase 4 (GPX4) inhibitor as a selective ferroptosis inducer. GPX4-IN-3 (26a) exhibits 71.7% inhibition for GPX4 with 1 μM.

Solasonine is a ferroptosis inducer which can be isolated from Solanum melongena that has anti-infection, anti-cancer, and neurogenesis promoting properties. Solasonine promotes ferroptosis of HCC cells via destruction of the glutathione redox system induced by inhibiting GPX4, and can be used for cancer research.

GPX4-IN-5 is a covalent inhibitor of GPX4 (IC₅₀: 0.12 μM). GPX4-IN-5 can induce ferroptosis and has anti-tumor effects. GPX4-IN-5 can be used in the study of triple-negative breast cancer (TNBC).

Pipecolic acid-d₉ is the deuterium labeled Pipecolic acid. Pipecolic acid is a metabolite of lysine and an important precursor for many useful microbial secondary metabolites. Pipecolic acid slows ferroptosis in diabetic retinopathy by inhibiting the YAP-GPX4 signaling pathway. In addition, Pipecolic acid can be used as a diagnostic marker for pyridoxine-dependent epilepsy.

GPX4-IN-4 (Compound 24) is a potent GPX4 inhibitor. GPX4-IN-4 can be used for the research of cancer.

Propiolamide is a monooxygenase (MMO) system activator and glutathione peroxidase 4 (GPX4) inhibitor. Propiolamide induces ROS production through interaction with the MMO system. Propiolamide promotes the accumulation of intracellular cytotoxic lipid peroxides and induces ferroptosis. Propiolamide induces programmed cell death via the apoptosis pathway. Propiolamide can be used in cancer research.

NPD4928, a GPX4 inhibitor, enhances RSL3 (HY-100218A)-dependent ferroptosis. NPD4928 binds to ferroptosis suppressor protein 1 (FSP1) and inhibits its enzymatic activity.

GPX4-IN-6 (Compound C25) is a GPX4 covalent inhibitor with an IC₅₀ value of 0.13 μM. GPX4-IN-6 (Compound C25) can induce ferroptosis for the research of triple-negative breast cancer (TNBC) .

JKE-1716 is a potent and selective nitrolic acid-containing GPX4 inhibitor. JKE-1716 is able of inducing ferroptosis selectively through covalent GPX4 inhibition.

GPX4-IN-1 is a potent GPX4 inhibitor. GPX4 shows antiproliferative activity. GPX4-IN-1 has the potential for the research of cancer.

GPX4-IN-9 (Compound A16) is a glutathione peroxidase 4 (GPX4) inhibitor that specifically targets GPX4 under both in vitro and in vivo conditions, inducing ferroptosis. GPX4-IN-9 exhibits cytotoxicity against pancreatic cancer cells and can be used in cancer research.

RSL3-NH2 hydrochloride is a GPX4 inhibitor and ferroptosis inducer. RSL3-NH2 hydrochloride triggers the iron-dependent cell death pathway associated with lipid peroxidation by inhibiting GPX4 activity. RSL3-NH2 hydrochloride exhibits significant cytotoxicity against colorectal cancer cells and effectively induces their ferroptosis. RSL3-NH2 hydrochloride can serve as a ADC payload for synthesizing a ADC and be used in colorectal cancer-related research.

NCI677397 is a USP24 inhibitor. NCI677397 increases lipid ROS, activates cholesterol and fatty acid biosynthesis, degrades ABC transporters, GPX4 and DHFR through the autophagy pathway, decreases the level of P-gp and ultimately leads to ferroptosis in drug-resistant cancer cells. NCI677397 can be used for the study of lung caner and brain cancer.