Ferroptosis

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.

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.

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 ferroptosis inducer with inhibitory effects on system Xc-cystine/glutamate transporter proteins. Imidazole ketone erastin has antitumor activity and induces glutathione depletion and lipid peroxidation.

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 ferroptosis and induces autophagy.

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.

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

NADPH tetrasodium salt is the reduced form of the electron acceptor nicotinamide adenine dinucleotide phosphate, which acts as an electron donor in a variety of biological reactions. NADPH tetrasodium salt is also an endogenous inhibitor of ferroptosis.

Sorafenib (Bay 43-9006) is a multikinase inhibitor that targets 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. It exhibits antitumor properties and can induce autophagy, apoptosis, and agonistic iron death.

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.

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

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

L-Buthionine-(S,R)-sulfoximine, a cell-permeable and irreversible inhibitor of γ-glutamylcysteine synthetase (Ki <100 μM), induces oxidative stress in cells by depleting GSH.

(-)-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.

Vamifeport (VIT-2763) is a novel orally active inhibitor that targets iron transport proteins and reduces markers of hemolysis in the SCD Townes model.VIT-2763 improves anemia and erythropoiesis, ameliorates vascular inflammation, and can be studied in β-thalassemia.

Nordihydroguaiaretic acid (NDGA) is a natural product, extracted from Pole Fork Kelaroa, and is a lipoxygenase (5-LOX) inhibitor (IC50=8 μM). Nordihydroguaiaretic acid possesses antioxidant and free radical scavenging properties.

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.

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.

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

Brusatol (NSC-172924) is a natural product isolated from the Brucea javanica plant. It inhibits Nrf2.

Roxadustat (FG-4592) is an orally bioavailable, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), with potential anti-anemic activity.

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.

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.

Troglitazone (Romglizone) is a PPARγ agonist with anti-inflammatory and anti-tumor activity.

PD146176 (NSC-168807) is an inhibitor of 15-Lipoxygenase (15-LO) , it inhibits rabbit reticulocyte 15-LO with Ki of 197 nM and IC50 of 0.54 μM. PD146176 reverses cognitive impairment, brain amyloidosis, and tau pathology by stimulating autophagy in aged triple transgenic mice.

Cycloheximide (Naramycin A) is a natural product that reversibly inhibits translation elongation, is an antimitotic compound, and is an inhibitor of DNA and protein synthesis.

Linagliptin (BI 1356) is a potent, orally bioavailable dihydropurinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity.

FIN56, a specific inducer of ferroptosis, is identified by its IUPAC name [1,3,8-trihydroxy-6-methylanthracen-9(10H)-one].

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

BODIPY 581 591 C11 is a fluorescent radioactive probe used to indicate lipid peroxidation and antioxidant efficacy in model membrane systems and living cells.

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.

Atorvastatin hemicalcium salt (Atorvastatin Calcium) is an HMG-CoA reductase inhibitor with oral activity. Atorvastatin hemicalcium salt is used to lower cholesterol.

Bay 11-7085 can irreversibly inhibit the IκBα phosphorylation induced by TNFα (IC50: 10 μM).

Baicalein (5,6,7-Trihydroxyflavone) is a xanthine oxidase inhibitor.

Trigonelline (Trigenolline), an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee.

Sulfasalazine (Azulfidine) is a synthetic salicylic acid derivative with affinity for elastin-containing connective tissues and formulated as a prodrug. Sulfasalazine induces iron death and inhibits NF-κB, TGF-β and COX-2.

Siramesine hydrochloride (Lu 28-179 hydrochloride) is a selective sigma-2 receptor agonist, which has been shown to trigger cell death of Y cells and to exhibit a potent anticancer activity in vivo.

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.

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

Deferasirox (CGP-72670) is an oral iron chelating agent used to treat chronic iron overload.

Piperazine erastin, an analog of erastin, induces ferroptosis, an iron-dependent form of non-apoptotic cell death.

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.

Cerivastatin is an orally active and highly effective HMG-CoA reductase inhibitor with anticancer and lipid-lowering effects. Cerivastatin can reduce low-density lipoprotein cholesterol levels, inhibit the proliferation and invasion of MDA-MB-231 cells, and can be used to study primary hyperlipidemia.

Eprenetapopt (PRIMA-1Met) restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1MET also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.

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.

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

Ciclopirox (HOE296b) exerts its action by binding to and chelating trivalent cations, such as Fe3+ and Al3+, thereby inhibiting the availability of essential co-factors for enzymes. Ciclopirox is a synthetic, broad-spectrum antifungal agent with additional antibacterial and anti-inflammatory activities. This may lead to a loss of activity of enzymes that are essential for cellular metabolism, the organization of cell wall structure and other crucial cell functions. In addition, ciclopirox exerts its anti-inflammatory activity by inhibiting 5-lipoxygenase and cyclooxygenase (COX).

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.