Ferroptosis Inducer

PGP/FSP1-IN-1 is a dual PGP and FSP1 inhibitor and ferroptosis inducer that inhibits the oxidoreductase activity of FSP1. PGP/FSP1-IN-1 competes with NAD (P) H for binding to the pocket of FSP1 and induces FSP1 self-assembly, thereby directly blocking the catalytic function of the relevant enzyme. PGP/FSP1-IN-1 promotes lipid peroxidation and significantly enhances cellular sensitivity to ferroptosis when GPX4 activity is impaired or glutathione synthesis is inhibited. PGP/FSP1-IN-1 can be used in cancer research.

STAT3-IN-40 (Compound 8b) is an anti-cancer agent. STAT3-IN-40 can trigger the immune responses of CD4+ and CD8+ T lymphocytes and induce ferroptosis and apoptosis of tumor cells by inhibiting the expression and phosphorylation of STAT3. STAT3-IN-40 can be used in the research of chemoimmunotherapeutic agents for cancer.

CYCS-INPP4A interaction-IN-1 (10A3) disrupts the CYCS-INPP4A interaction complex and enhances ferroptosis-mediated tumor suppression.

NSCLC-IN-1 (Compound A10-2) induces mitophagy and ferroptosis through targeting transmembrane BAX inhibitor motif containing 6 (TMBIM6). NSCLC-IN-1 induces mitochondrial Ca²⁺ imbalance, leading to mitochondrial damage. NSCLC-IN-1 reduces intracellular glutathione (GSH), increases the accumulation of lipid peroxides (LPO) and malondialdehyde (MDA) content. NSCLC-IN-1 is a potent anti-NSCLC agent.

Myrislignan-13C,d2 is the ¹³C, d₂ deuterated-labeled Myrislignan (HY-N0608). 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.

Antitumor agent-156 (Compound 20) causes DNA damage and mitochondrial dysfunction, promotes reactive oxygen species generation, activates endoplasmic reticulum stress, and induce apoptosis, autophagy and ferroptosis. Antitumor agent-156 shows superior antitumor activity against cancer cells including Cisplatin (HY-17394) resistance cells. Antitumor agent-156 displayS good liver-targeting ability.

OXPHOS-IN-3 is a mitochondria-targeted dual OXPHOS/glycolysis inhibitor. OXPHOS-IN-3 exhibits potent antiproliferative activity against pancreatic cancer cells. OXPHOS-IN-3 induces mitochondrial dysfunction, ferroptosis, and immunogenic cell death (ICD). OXPHOS-IN-3 shows potent antitumor activity in pancreatic ductal adenocarcinoma (PDAC) models.

Ferroptosis inducer-8 is a ferroptosis inducer with high selectivity for other cell death mechanism. Ferroptosis inducer-8 induces ferroptosis by affecting ACSL4, GPX4, and FTH1, thereby disrupting intracellular iron homeostasis and the GSH/GPX4 antioxidant defense system, ultimately leading to the accumulation of lipid peroxidation. Ferroptosis inducer-8 also induces ROS production. Ferroptosis inducer-8 inhibits tumor growth and can be used for research of triple-negative breast cancer (TNBC).

GPX4-IN-20, a Arctigenin (HY-N0035) derived, is a GPX4& molecular gluedegrader. GPX4-IN-20 induces ferroptosis by increasing lipid ROS levels and suppressing GSH levels. GPX4-IN-20 reduces the protein expression and enzyme activity of GPX4 in a dose-dependent manner without affecting other ferroptosis-related proteins. GPX4-IN-20 induces ubiquitination-dependent proteasomal degradation of GPX4. GPX4-IN-20 also increases the level of malondialdehyde (MDA) in HCT-116 cells. GPX4-IN-20 can be used for the research of colorectal cancer.

GPX4-IN-10 (compound I20) is a non-covalent GPX4 inhibitor. GPX4-IN-10 induces ferroptosis and inhibits cell growth of HT1080 cells.

PROTAC GPX4 degrader-5 (compound N15) is an efficient and highly selective PROTAC GPX4 degrader (DC₅₀ = 28 nM). PROTAC GPX4 degrader-5 can induce ferroptosis and has low toxicity to normal cells. PROTAC GPX4 degrader-5 can significantly increase ROS. PROTAC GPX4 degrader-5 exerts anti proliferative effects on various tumor cells. PROTAC GPX4 degrader-5 is commonly used in cancer research.

Ferroptosis/apoptosis inducer-4 is a pyridine-hydrazone-derived Cu (II) complex and a synergistic inducer of ferroptosis and apoptosis. Ferroptosis/apoptosis inducer-4 exerts anti-tumor proliferation and anti-metastasis effects with extremely low systemic toxicity. Ferroptosis/apoptosis inducer-4 disrupts cellular redox homeostasis by depleting glutathione and generating hydroxyl radicals through the Cu²⁺/Cu⁺ redox cycle. Ferroptosis/apoptosis inducer-4 also triggers mitochondrial dysfunction and endoplasmic reticulum stress, which in turn lead to Ca²⁺ release, mitochondrial Ca²⁺ overload, and the formation of a ROS−Ca²⁺ self-amplifying feedback loop. Ferroptosis/apoptosis inducer-4 can be used in studies related to cervical cancer.

CIB-Q22 is a potent pyruvate carboxylase (PC) inhibitor with an IC₅₀ of 1.74 nM. CIB-Q22 suppresses hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion. CIB-Q22 induces apoptosis and ferroptosis, promotes mitochondrial oxidative stress and dysfunction, inhibits glycolysis and anaplerotic flux, and reverses epithelial-mesenchymal transition (EMT). CIB-Q22 can be used for the study of hepatocellular carcinoma.

Antitumor agent-78 is an antitumor agent, inhibits cancer cells growth and migration. Antitumor agent-78 triggers ferroptosis by inhibiting GPx-4 and elevating COX2. Antitumor agent-78 also activates intrinsic apoptotic pathway (Bax-Bcl-2-caspase-3) and hinders Epithelial-mesenchymal transition (EMT) process of cancer cells.

BG11 induces the accumulation of Fe²⁺ and intracellular lipid peroxides, induces ferroptosis. BG11 regulates the expression of Bax and Bcl-2 proteins, and induces apoptosis in MDA-MB-231 cell. BG11 arrests the cell cycle at G0/G1 and S phase, inhibits the proliferation of TNBC cancer cell (IC₅₀ for MDA-MB-231 and BT549 is 0.49 μM and 0.52 μM), and inhibits the cell migration and invasion. BG11 exhibits antitumor efficacy in mouse models.

GPX4-IN-21 (Compound 4d) is a selective glutathione peroxidase 4 (GPX4) inhibitor. GPX4-IN-21 can induce ferroptosis and downregulate the ferroptosis-related proteins SLC7A11, SLC11A2 and GPX4 levels. GPX4-IN-21 can induce ROS and MDA accumulation GPX4-IN-21 exhibits potent anti-proliferative activity. GPX4-IN-21 can be used for the research of cancer, such as melanoma.

EGFR-IN-178 is an orally active EGFR mutant inhibitor, exhibits highly selective inhibitory activity against mutants of the EGFR enzyme, including Del19 (IC₅₀ = 3.4 nM), L858R/T790 M (IC₅₀ = 2.9 nM), and Del19/T790 M (IC₅₀ = 2.5 nM). EGFR-IN-178 has good activity against JAK2 (IC₅₀ = 55.6 nM) and JAK3 (IC₅₀ = 46.1 nM) kinases. EGFR-IN-178 can increase cellular lipid oxide MDA, meanwhile decrease GSH content, causing ferroptosis in cancer cells. EGFR-IN-178 promotes apoptosis by increasing cleaved caspase-3 expression. EGFR-IN-178 can inhibit the phosphorylation of EGFR protein and decrease the active form p-JAK2 for JAK2, induce an increase in intracellular ROS. EGFR-IN-178 can be used for the study of non-small cell lung cancer (NSCLC).

Ferroptosis inducer-13 is a 5′-prenylated chalcone derivative that effectively induces ferroptosis in human non-small cell lung cancer (NSCLC) cells by altering the activity of the Nrf2/xCT/GPX4 pathway. Ferroptosis inducer-13 exhibits potent anti-proliferative effects in vitro, and inhibits tumour growth in a NSCLC mouse model. Ferroptosis inducer-13 can be used for NSCLC research.

FGFR-IN-27 is an orally active, broad-spectrum FGFR inhibitor, with an IC₅₀ of 0.24 nM against human FGFR1, 0.71 nM against FGFR2, 0.87 nM against FGFR3, and 6.50 nM against FGFR4. FGFR-IN-27 inhibits cancer cell proliferation and blocks tumor growth. FGFR-IN-27 reduces the phosphorylation levels of AKT and ERK, induces apoptosis and ferroptosis, increases ROS levels, and decreases GSH levels. FGFR-IN-27 can be used in the research of hepatocellular carcinoma.

PAA4 is a hypercoordinate carbon-centered tetranuclear gold (I) cluster prodrug. PAA4 releases active Au (I) ions upon triggering by GSH (HY-D0187), and this process is accelerated in the acidic microenvironment of bladder cancer cells with high GSH expression. PAA4 inhibits the activities of cytosolic TrxR1 and mitochondrial TrxR2, inducing ROS accumulation, lipid peroxidation, ferroptosis, loss of mitochondrial membrane potential and DNA damage. PAA4 can be used in bladder cancer-related research.