Ferroptosis inducer (FIN)

A ferroptosis inducer is a pharmacological agent or small molecule designed to trigger ferroptosis, a regulated form of iron-dependent cell death characterized by the lethal accumulation of lipid hydroperoxides [1, 11]. Rather than representing a single protein or receptor target, the term 'ferroptosis inducer' refers to a functional class of compounds (e.g., Erastin, RSL3) that target various nodes of the cellular antioxidant network, most notably the System Xc- transporter and Glutathione peroxidase 4 (GPX4) [2, 6]. In drug development, these inducers are particularly promising for oncology, as they can bypass traditional apoptosis resistance and target drug-tolerant or mesenchymal-state cancer cells that are intrinsically vulnerable to iron-mediated oxidative stress [3, 5, 8]. However, because the term describes a functional outcome rather than a specific biological target molecule, it is considered a pharmacological classification [12, 18]. The therapeutic use of such agents must balance potent anti-tumor activity against the risk of inducing oxidative injury in non-malignant tissues or worsening neurodegenerative conditions [13, 17].

Other names

Ferroptosis-inducing agentPro-ferroptotic agentFerroptosis activatorIron-dependent cell death agent

Ferroptosis inducers (FINs) typically trigger cell death through four major classes of action: Class I inducers (e.g., Erastin) inhibit the System Xc- cystine/glutamate transporter, leading to cysteine deprivation and glutathione (GSH) depletion; Class II inducers (e.g., RSL3) directly inhibit Glutathione peroxidase 4 (GPX4) activity; Class III inducers (e.g., FIN56) deplete GPX4 protein via degradation or synthesis inhibition; and Class IV inducers (e.g., FINO2) promote iron-dependent lipid peroxidation through non-enzymatic pathways or Coenzyme Q10 depletion [3, 6, 11, 15].