Ferroptosis Activator

Cisplatin (CDDP) is an antineoplastic chemotherapy agent by cross-linking with DNA and causing DNA damage in cancer cells. Cisplatin activates ferroptosis and induces autophagy.

Erastin is a ferroptosis inducer. Erastin exhibits the mechanism of ferroptosis induction related to ROS and iron-dependent signaling. Erastin inhibits voltage-dependent anion channels (VDAC2/VDAC3) and accelerates oxidation, leading to the accumulation of endogenous reactive oxygen species. Erastin also disrupts mitochondrial permeability transition pore (mPTP) with anti-tumor activity. Furthermore, Erastin can block the uptake of cystine mediated by SLC7A11 and also spares UMRC6-EV and -C91A cells from disulfidptosis under glucose starvation.

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.

ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor with an IC₅₀ of 1.9 μM.

Simvastatin (MK 733) is a competitive inhibitor of HMG-CoA reductase with a K_i of 0.2 nM.

Hemin is an iron-containing porphyrin. Hemin is an Heme oxygenase (HO)-1 inducer.

L-Glutamic acid is an excitatory amino acid neurotransmitter that acts as an agonist for all subtypes of glutamate receptors (metabolic rhodophylline, NMDA, and AMPA). L-Glutamic acid has an agonist effect on the release of DA from dopaminergic nerve endings. L-Glutamic acid can be used in the study of neurological diseases. L-Glutamic acid acts at ionotropic and metabotropic glutamate receptors.

Roxadustat is an orally active hypoxia-inducible factor prolyl-hydroxylase (PHD) inhibitor (HIF-PHI) that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin.

Pifithrin-α hydrobromide is a p53 inhibitor which blocks its transcriptional activity and prevents cells from apoptosis. Pifithrin-α hydrobromide is also an aryl hydrocarbon receptor (AhR) agonist.

Lapatinib (GW572016) is a potent, orally active inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC₅₀ values against purified EGFR and ErbB-2 of 10.2 and 9.8 nM, respectively.

Lovastatin (Mevinolin) is a cell-permeable HMG-CoA reductase inhibitor used to lower cholesterol.

Sulfasalazine (NSC 667219) is an anti-rheumatic agent for the research of rheumatoid arthritis and ulcerative colitis. Sulfasalazine can suppress NF-κB activity. Sulfasalazine is a type 1 ferroptosis inducer.

L-Buthionine-(S,R)-sulfoximine is a cell-permeable, potent, fast acting and irreversible inhibitor of g-glutamylcysteine synthetase and depletes cellular glutathione levels. The IC₅₀ value of L-Buthionine-(S,R)-sulfoximine on melanoma, breast and ovarian tumor specimens are 1.9 μM, 8.6 μM, and 29 μM, respectively.

Artesunate is an inhibitor of both STAT-3 and exported protein 1 (EXP1).

TBHQ (tert-Butylhydroquinone) is a widely used Nrf2 activator, protects against Doxorubicin (DOX)-induced cardiotoxicity through activation of Nrf2. TBHQ (tert-Butylhydroquinone) is also an ERK activator; rescues Dehydrocorydaline (DHC)-induced cell proliferation inhibitionin melanoma.

DL-Buthionine-(S,R)-sulfoximine is a potent inhibitor of glutamylcysteine synthetase biosynthesis.

iFSP1 is a potent, selective and glutathione-independent inhibitor of ferroptosis suppressor protein 1 (FSP1) (AIFM2) with an EC₅₀ of 103 nM. iFSP1 selectively induces ferroptosis in GPX4-knockout cells which overexpressed FSP1. iFSP1 is able to sensitize a variety of human cancer cell lines to the ferroptosis inducer, such as (1S,3R)-RSL3 (HY-100218A).

Gallic acid (3,4,5-Trihydroxybenzoic acid) is a natural polyhydroxyphenolic compound and an free radical scavenger to inhibit cyclooxygenase-2 (COX-2). Gallic acid has various activities, such as antimicrobial, antioxidant, antimicrobial, anti-inflammatory, and anticance activities.

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.

Artemisinin (Qinghaosu), a sesquiterpene lactone, is an anti-malarial agent isolated from the aerial parts of Artemisia annua L. plants. Artemisinin inhibits AKT signaling pathway by decreasing pAKT in a dose-dependent manner. Artemisinin reduces cancer cell proliferation, migration, invasion, tumorigenesis and metastasis and has neuroprotective effects.