Ferroptosis Inducer

Ironomycin is a derivative of Salinomycin (HY-15597). Ironomycin exhibits selective inhibitory activity against mantle cell lymphoma (MCL) cells. Ironomycin blocks the cell cycle and induces apoptosis and ferroptosis. Ironomycin induces double-strand DNA breaks and activates the unfolded protein response (UPR), particularly the IRE1α signaling pathway accumulation. The combination of Ironomycin with Ibrutinib (HY-10997) shows a synergistic effect. Ironomycin can be used for the study of MCL.

MT-125 free base is a specific and well-tolerated inhibitor of non-muscle myosin IIA (K_i,NMIIA = 2.7 μM) and IIB (EC₅₀ = 1.7 μM). MT-125 free base can pass through the blood-brain barrier. MT-125 free base induces ferroptosis and DNA damage by increasing the levels of reactive oxygen species (ROS) within tumor cells. MT-125 free base can enhance the PDGFR signaling pathway. MT-125 free base can be used for research on glioblastoma.

iMQT_020 is a selective allosteric SLC1A5_var inhibitor. iMQT_020 disrupts the trimeric assembly of SLC1A5_var, causing metabolic crisis in cancer cells and selectively suppressing their growth. iMQT_020 reduces glutamine anaplerosis and oxidative phosphorylation, resulting in a broad disruption of cancer metabolism. iMQT_020 reduces GSH levels and increases cellular ROS and mitochondrial ROS. iMQT_020 induces apoptosis and ferroptosis. iMQT_020 can epigenetically upregulate PD-L1 expression. iMQT_020 can be used for the study of pancreatic cancer, lung cancer, and colon cancer.

ROS-generating agent 1 is a selective ROS-generating agent. ROS-generating agent 1 inhibits TrxR activity and expression in cancer cells. ROS-generating agent 1 induces ROS-dependent apoptosis and ferroptosis in cancer cells. ROS-generating agent 1 selectively kills lung cancer cells and inhibits the growth of cancer cell xenograft tumors in nude mice. ROS-generating agent 1 can be used for the research of non-small cell lung cancer.

W1131 is a potent STAT3 inhibitor, triggering ferroptosis. W1131 suppresses cancer progression in gastric cancer cell subcutaneous xenograft model, organoids model, and PDX model. W1131 effectively alleviates chemical resistance of cancer cells to 5-FU (HY-90006). W1131 regulates cell cycle, DNA damage response, and oxidative phosphorylation, including IL6-JAK-STAT3 pathway and ferroptosis pathway.

Gigantol is an orally active bibenzyl compound. Gigantol targets MYC to promote its ubiquitin-proteasomal degradation and inhibit the growth of lung cancer cells. Gigantol exerts anti-lung cancer activity by inducing ferroptosis (Ferroptosis) via the SLC7A11-GPX4 axis. Gigantol restores the sensitivity of mcr-harboring multidrug-resistant bacteria to colistin. Gigantol ameliorates carbon tetrachloride-induced liver injury by inhibiting the activation of the JNK/cPLA2/12-LOX inflammatory pathway. Gigantol promotes cholesterol metabolism and progesterone biosynthesis in Leydig cells. Gigantol can be used in studies related to diseases such as lung cancer, multidrug-resistant Gram-negative bacterial infections, and acute liver injury.

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.

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.

Ferrous gluconate is a highly water-soluble iron-containing agent with high bioavailability and bactericidal activity. As a non-heme iron, Ferrous gluconate is used for meat product fortification and improvement of iron deficiency anemia. Ferrous gluconate induces ferroptosis in E. coli through Fe²⁺ infiltration, reactive oxygen species burst, lipid peroxidation and direct interaction with DNA. Ferrous gluconate also downregulates the SOS responsive transcriptional repressor LexA. In addition, Ferrous gluconate regulates multiple key pathways in E. coli such as fatty acid metabolism, iron-sulfur cluster assembly and pyruvate metabolism, and is applied in studies related to *E. coli* infection and iron deficiency anemia.

CT-1 is a secreted protein belonging to the IL-6 cytokine family. Overexpression of CT-1 enhances cell proliferation, migration and angiogenesis via the ADMA/DDAH pathway. CT-1 inhibits the growth of triple-negative breast cancer cells by simultaneously inducing Ferroptosis in N2-type tumor-associated neutrophils and cancer cells. CT-1 activates the Jak/STAT-3, p42/p44 MAPK and AMPK pathways, and inhibits GSK-3β activity through phosphorylation to induce cardiomyocyte hypertrophy. CT-1 enhances the viability of cardiomyocytes and neurons, reduces cell Apoptosis, induces the expression of heat shock proteins (HSP) and BNP, and inhibits TNF levels. CT-1 exerts anti-tumor activity in mouse models of triple-negative breast cancer. CT-1 improves cognitive impairment in mice. CT-1 is applicable to the research of ischemic heart disease, triple-negative breast cancer, myocardial hypertrophy, Parkinson's disease, hypertensive heart disease, myocardial infarction, acute Chagas cardiomyopathy, high-fat diet-induced cognitive impairment and diabetes-related cognitive impairment.

1-Palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine is an oxidized phospholipid. 1-Palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine reduces the viability of HUVECs, increases the levels of ferrous ions and lipid peroxidation, promotes the production of superoxide anions, and decreases the levels of glutathione and GPX4 in cells. 1-Palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine upregulates the mRNA and protein levels of FABP3 in HUVECs, impairs mitochondrial membrane potential, and induces ferroptosis-related changes as well as mitochondrial dysfunction and damage. 1-Palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine activates caspase-11 and promotes the continuous release of IL-1β from macrophages and dendritic cells. 1-Palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine inhibits the proliferation of aortic smooth muscle cells and induces apoptosis in these cells. 1-Palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine is applicable to relevant research on atherosclerosis.

Diphenyl disulfide (Phenyl disulfide) is an organic disulfide compound. Diphenyl disulfide inhibits the PI3K/AKT/mTOR pathway, and induces ferroptosis (ferroptosis), apoptosis (apoptosis) and autophagy (autophagy) in cancer cells. Diphenyl disulfide downregulates GPX4 expression, inhibits NRF2 phosphorylation, induces lipid peroxidation, promotes xCT ubiquitination, induces proteolytic cleavage of p21 Bax into p18 Bax, and suppresses cell proliferation and viability. Diphenyl disulfide can be used in research related to melanoma and breast cancer.

6-Methoxydihydrosanguinarine is an alkaloid with activity across multiple cancer cell types. 6-Methoxydihydrosanguinarine activates IRE1/JNK signaling, blocks Akt/mTOR and PI3K/AKT/mTOR pathways, reduces expression of Cdc25C, CyclinB1, Cdc2, YAP/TAZ, Survivin, GPX4, and EGFR, upregulates IRE1 and DR5, and activates JNK and caspases. 6-Methoxydihydrosanguinarine induces apoptosis, G2/M phase arrest, DNA damage, ROS generation, lipid peroxidation, ferroptosis, autophagy, and suppresses cancer cell growth. 6-Methoxydihydrosanguinarine disruptes the biofilm formation of Candida albicans (C. albicans). 6-Methoxydihydrosanguinarine can be used for the research of non-small cell lung cancer, hepatocellular carcinoma, melanoma, colon carcinoma, ovarian cancer and breast cancer.

Nrf2-IN-4 (Compound PhcY) hydrobromide is a Nrf2 inhibitor. Nrf2-IN-4 hydrobromide induces ferroptosis via NRF2 inhibition. Nrf2-IN-4 hydrobromide disrupts cellular iron homeostasis, facilitates ferritin degradation, and ultimately triggers ferroptosis. Nrf2-IN-4 hydrobromide induces lysosome activation by promoting iron-dependent ROS production and lysosomal acidification. Nrf2-IN-4 hydrobromide demonstrates significant antitumor efficacy. Nrf2-IN-4 hydrobromide can be used for the study of breast cancer.

Myrislignan is a PI3K/AKT/NF-κB inhibitor that can cross the blood-brain barrier. Myrislignan exerts anticancer activity by inducing apoptosis and ferroptosis. Myrislignan inhibits the replication and invasion of Toxoplasma gondii; it induces reactive oxygen species (ROS) imbalance, autophagy, and the death of Toxoplasma gondii tachyzoites. Myrislignan inhibits mitochondrial function and ERK1/2 phosphorylation to improve ovariectomy-induced osteoporosis. Myrislignan can be used in studies related to gastric cancer, glioblastoma, osteoporosis, and toxoplasmosis.

Macranthoside B is an apoptosis inducer with in vitro and in vivo anticancer activity. Macranthoside B induces autophagy and ferroptosis in cancer cells. Macranthoside B induces intracellular ROS accumulation, activates AMPK, inhibits mTOR and P70S6 kinase phosphorylation, and modulates Bcl-2/Bax expression. Macranthoside B activates caspase-3, caspase-9, and the intrinsic caspase cascade, induces PARP cleavage/degradation, and inhibits NRF2 signaling. Macranthoside B disrupts iron homeostasis via NCOA4-dependent ferritinophagy, up-regulates Lip-ROS, reduces mitochondrial membrane potential, and activates the JNK pathway. Macranthoside B can be used for the research of ovarian cancer, hepatoma, gastric carcinoma, breast carcinoma, colon carcinoma, glioma, melanoma, adenocarcinoma of the esophagogastric junction, and cervical cancer.

DIM-3,5-Cl2 is an inverse NR4A1/NR4A2 agonist with K_D values of 7.7 μM and 12.0 μM for NR4A1 and NR4A2, respectively. DIM-3,5-Cl2 acts as an inverse agonist to downregulate pro-oncogenic and proendometriotic gene products, and as an agonist to enhance NR4A1/2/Sp1/Sp4-mediated CD71 transactivation. DIM-3,5-Cl2 induces ferroptosis via ROS formation, lipoperoxidation, MDA production, and reduced GPX4, SLC7A11 expression. DIM-3,5-Cl2 induces apoptosis via PARP and caspase-3 cleavage, reduced BCL-2 expression, and inhibits cancer cell viability. DIM-3,5-Cl2 can be used for the research of triple negative breast cancer, endometriosis, and colorectal cancer.

Agrimonolide is a phenethyl isocoumarin compound discovered from Agrimonia pilosa, exhibiting anti-inflammatory, antioxidant, and anticancer activities. Agrimonolide inhibits NF-κB, MAPK, and TLR4-mediated neuroinflammatory signaling, suppresses Notch and JAK2/STAT3 signaling to modulate Th17/Treg balance and maintain the intestinal barrier. Agrimonolide decreases HIF1A expression, inhibits glycolysis, and induces ferroptosis and cell cycle arrest via the mTOR pathway in tumor models, thereby suppressing cancer cell viability, proliferation, and metastasis. Agrimonolide exerts hepatoprotective and anti-fibrotic effects by regulating bile acid transporter expression and reducing hepatic bile acid accumulation. Agrimonolide is used for research on ulcerative colitis, ovarian cancer, non-small cell lung cancer, cholestatic liver injury, and neuroinflammation.

Ferroptosis inducer-2 (Compound 24) is an inducer for heme oxygenase-1 (HO-1). Ferroptosis inducer-2 exhibits anticancer activity against triple-negative breast cancer (TNBC) cells through induction of ferroptosis.

SKLB-D18 is an orally active ERK1/2/ERK5 inhibitor, with an IC₅₀ of 38.69 nM and a K_d of 126.9 nM against human ERK1, an IC₅₀ of 40.12 nM and a K_d of 209.8 nM against ERK2, and an IC₅₀ of 59.72 nM and a K_d of 468.2 nM against ERK5. SKLB-D18 inhibits cancer cell proliferation, induces G0/G1 cell cycle arrest and apoptosis. SKLB-D18 reduces the levels of p-ERK5, p-RSKp90, p-c-Myc and c-Myc, and upregulates the level of p-ERK1/2, thereby inhibiting the ERK1/2/5 pathway in cells. SKLB-D18 increases LC3B-II accumulation, and decreases the levels of p62, p-mTOR and p-p70S6K. SKLB-D18 elevates the levels of ROS, lipid peroxidation and free ferrous ions, reduces the levels of NCOA4 and GPX4, and induces ferritin autophagy-dependent ferroptosis in cancer cells. SKLB-D18 exhibits antitumor activity in a triple-negative breast cancer xenograft mouse model. SKLB-D18 can be used in research related to triple-negative breast cancer.