Ferroptosis

Cisplatin (CDDP) is a DNA cross-linking agent. Cisplatin has antitumor activity and inhibits DNA synthesis by forming DNA adducts in cancer cells. Cisplatin also activates iron death and induces autophagy.

Curcumin (Natural Yellow 3) is a phenolic natural product, an inhibitor of histone acetyltransferase p300/CREB (IC50=25 μM) with specificity. Curcumin has a wide range of pharmacological activities such as antitumor, anti-inflammatory and antioxidant.

Sorafenib (Bay 43-9006) is a multikinase inhibitor that inhibits Raf-1, B-Raf, VEGFR2, VEGFR3, VEGFR4, PDGFRβ, FLT3, c-Kit, and others (IC50=6/22/90/15/20/20/57/58 nM) with oral activity. Sorafenib has antitumor activity and can induce autophagy and apoptosis as well as agonistic iron death.

Erastin is an iron death activator that acts on the mitochondrial VDAC in a ROS- and iron-dependent manner. Erastin has anti-tumor activity and acts selectively on tumor cells with RAS-carcinogenic mutations. The product is unstable in solution and is recommended to be dispensed now.

ML385 is an NRF2 inhibitor (IC50=1.9 μM) with novelty and specificity. ML385 has anti-inflammatory activity by modulating anti-oxidative stress through the inhibition of NRF2. ML385 also exhibits anti-tumor activity.

Deferoxamine Mesylate (DFOM) is an iron chelator and iron death inhibitor. Deferoxamine Mesylate binds free iron into a stable complex and reduces iron accumulation. Deferoxamine Mesylate up-regulates HIF-1α levels and induces apoptosis.

Ferrostatin-1 (Fer-1) is a potent and selective inhibitor of iron death. Ferrostatin-1 potently inhibits Erastin-induced iron death in HT-1080 cells with an EC50 of 60 nM. Ferrostatin-1 also exhibits antioxidant and antifungal activities.

Imidazole ketone erastin (IKE) is an iron death inducer with inhibitory effects on system Xc-cystine/glutamate transporter proteins. Imidazole ketone erastin has antitumor activity and induces glutathione depletion and lipid peroxidation.

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 iron death that is selective for tumor cells carrying oncogenic RAS.

Liproxstatin-1 is a potent and selective inhibitor of iron death (IC50=22 nM). Liproxstatin-1 protects cells from iron death induced by iron death inducers (e.g., Erastin, RSL3).

Necrostatin-1 (Nec-1) is a necrotic apoptosis inhibitor and RIP1 inhibitor with specificity. Necrostatin-1 inhibits TNF-α-induced necrotic apoptosis. Necrostatin-1 also inhibits IDO.

trans-3-Indoleacrylic acid is one of the endogenous metabolites that inhibits RSL3-induced iron death and can be used to study colorectal cancer.

Dopamine hydrochloride (ASL279) is a naturally occurring catecholamine formed by decarboxylation of dihydroxyphenylalanine and a precursor of norepinephrine and epinephrine. Dopamine hydrochloride binds to alpha-1- and beta-1- adrenergic receptors.

L-Glutamine (L-Glutamic acid 5-amide) , a non-essential amino acid, is synthesized from glutamic acid and ammonia.

L-Glutamic acid (Glutaminol) acts as an excitatory transmitter, shows a direct activating effect on the release of DA from dopaminergic terminals.

Coenzyme Q10 (CoQ10) (ubiquinone) is a naturally occurring compound, acting as the electron carrier in the mitochondrial respiratory chain.

Vildagliptin (LAF237) is a cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Vildagliptin's cyano moiety undergoes hydrolysis and this inactive metabolite is excreted mainly via the urine.

α-Vitamin E (Dexrabeprazole Sodium) is a naturally-occurring form of vitamin E, a fat-soluble vitamin with potent antioxidant properties.

L-Cystine (Cystine Acid) is not considered one of the 20 amino acids, L-Cystine (Cystine Acid) is a sulfur-containing derivative obtained from oxidation of cysteine amino acid thiol side chains. It functions as an antioxidant and protects tissues against radiation and pollution, slowing the aging process. It also aids protein synthesis. L-Cystine (Cystine Acid) is abundant in many proteins of skeletal tissues and skin, and found in insulin and digestive enzymes chromotrypsinogen A, papain, and trypsinogen.

L-Glutamic acid monosodium salt (MSG) (Monosodium glutamate) is an activator of mGlu1 receptor.

Gallic acid (Benzoic acid) is found in almost all plants. Plants known for their high gallic acid content include gallnuts,grapes,tea,hops and oak bark.

Artemisinin (Qinghaosu) is an ancient Chinese herbal therapy for malarial fevers which has been recently found to have potent activity against many forms of malarial organisms, including chloroquine-resistant Plasmodium falciparum.

Lapatinib (GW572016) is an inhibitor of ErbB2 and EGFR (IC50=9.2/10.8 nM) with oral activity. Lapatinib has antitumor activity and can be used to treat advanced or metastatic breast cancer with HER2 overexpression.

(-)-Epicatechin (Epicatechin) is an inhibitor of cyclooxygenase-1 (COX-1), inhibiting the IL-1β-induced expression of iNOS by blocking the nuclear localization of the p65 subunit of NF-κB.

Ammonium iron(III) citrate (Ferric ammonium citrate) is a physiological form of non-ferritin-bound iron that causes intracellular iron overload leading to cellular iron death and enhances protein production.

FA16 is a selective, metabolically stable ferroptosis inducer with an IC50 value of 1.26 μM.FA16 is a derivative of 2-(trifluoromethyl)benzimidazole.FA16 inhibits the cystine/glutamate inverse transporter protein (system Xc-)-mediated exchange of intracellular glutamate for extracellular cystine.FA16 significantly inhibited tumor growth in a HepG2 xenograft tumor model. HepG2 xenograft tumor model significantly inhibited tumor growth.

PRLX-93936 HCL is an analog of erastin and demonstrated synergistic effects against non-small cell lung cancer (NSCLC) cells with cisplatin.

FIN56 is a specific inducer of ferroptosis.

Zileuton (A 64077) is a synthetic derivative of hydroxyurea with antiasthmatic properties. The leukotriene inhibitor zileuton blocks 5-lipoxygenase, which catalyzes the formation of leukotrienes from arachidonic acid; causes bronchodilation; decreases bronchial mucous secretion and edema; and may prevent or decrease the symptoms of asthma.

Pravastatin sodium (CS-514 (sodium)), an HMG-CoA reductase inhibitor, inhibits sterol synthesis with IC50 of 5.6 μM.

Lovastatin (MK-803) is an HMG-CoA Reductase Inhibitor, used for lowering cholesterol.

Trolox is a vitamin E analogue, used in reducing oxidative stress or damage.

FINO2 is a potent ferroptosis-inducing compound that inhibits GPX4 activity. It functions as a stable oxidant, effectively oxidizing ferrous iron and demonstrating stability across varying pH levels. Furthermore, FINO2 induces widespread lipid peroxidation.

SP600125 (JNK Inhibitor II) is a JNK inhibitor that inhibits JNK1, JNK2, and JNK3 (IC50=40/40/90 nM) with oral potency, reversibility, and ATP-competitive properties. SP600125 inhibits autophagy and induces apoptosis.

Rosiglitazone (BRL49653) is a PPARγ agonist, TRPC5 activator, and TRPM3 inhibitor with oral activity. Rosiglitazone is also a hypoglycemic agent and a thiazolidinedione insulin sensitizer.

iFSP1, a potent, selective, and glutathione-independent ferroptosis suppressor protein 1 (FSP1) (AIFM2) inhibitor with an EC50 of 103 nM, sensitizes diverse human cancer cell lines to ferroptosis inducers like (1S,3R)-RSL3. It uniquely triggers ferroptosis in GPX4-knockout cells overexpressing FSP1.

Pifithrin-β hydrobromide (Cyclic PFT-α) is an inhibitor of p53; reversibly blocks p53-dependent transcriptional activation and apoptosis. Protects against neuronal death in models of stroke and neurodegenerative disorders. Active in vivo; protects mice from the side-effects of Y therapy associated with p53 induction. Supresses self-renewal of embryonic stem cells. Also aryl hydrocarbon receptor (AHR) agonist, causes upregulation of AHR target gene CYP1A1 (EC50 = 1.1 μM).

Pioglitazone (U 72107) is an insulin sensitizing agent and thiazolidinedione that is indicated for the treatment of type 2 diabetes. Pioglitazone has been linked to rare instances of acute liver injury.

U-73122 (U73122) , an effective PLC inhibitor, reduces agonist-induced Ca2+ increases in platelets and PMN.

Nordihydroguaiaretic acid (NDGA) (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It is a recognized inhibitor of lipoxygenase (LOX) and has antioxidant and free radical scavenging properties.

WITHAFERIN A is a novel class of NFkappaB inhibitors, which hold promise as novel anti-inflammatory agents for treatment of various inflammatory disorders and/or cancer.

L-Glutathione reduced (Glutathione) is a naturally occurring tripeptide found in cells as an endogenous antioxidant that scavenges oxygen free radicals. L-Glutathione reduced is a cofactor for certain enzymes and is involved in the rearrangement of protein disulfide bonds and the reduction of peroxides.

Bardoxolone Methyl (TP-155) is a synthetic triterpenoid that acts as an activator of the Nrf2 pathway and an inhibitor of the NF-κB pathway with potential anti-tumor and anti-inflammatory activities.

Sulfasalazine (Azulfidine) is a synthetic salicylic acid derivative with affinity for connective tissues containing elastin and formulated as a prodrug

Acetylcysteine (NAC) is an N-acetyl derivative of cysteine, a ROS inhibitor and mucolytic agent. Acetylcysteine induces apoptosis, can be used to reduce mucus thickness, and has anti-influenza viral activity.

UAMC-3203 hydrochloride is a potent and selective Ferroptosis inhibitor with an IC50 of 12 nM.

Artesunate (WR-256283) is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection. It is on the World Health Organization's List of Essential Medicines.

Pifithrin-α hydrobromide (Pifithrin-α hydrobromide) is a p53 inhibitor, inhibiting p53-dependent transactivation of p53-responsive genes.

CIL56 (CA3) is a small molecule that induces cellular ferroptosis through the production of iron-dependent reactive oxygen species (ROS). It also induces accumulation of long-chain saturated, monounsaturated, and polyunsaturated fatty acids in HT-1080 cells in vitro.HT-1080 cells lacking acetyl-CoA carboxylase 1 (ACC1), the rate-limiting enzyme in fatty acid synthesis, exhibit 5-fold resistance to CIL56 treatment, indicating ACC1 activity sensitizes cells to CIL56-induced cell death.

Simvastatin (MK 733) is an HMG-CoA reductase inhibitor (Ki=0.2 nM) with oral activity. Simvastatin has hypolipidemic activity, inhibits hepatic production of cholesterol, and is also used for the prevention of cardiovascular disease.