Bioinorganic Modulators of Ferroptosis: A Review of Recent Findings

Abstract

Ferroptosis was first reported as a separate modality of regulated cell death in 2008 and distinguished under its current name in 2012 after it was first induced with erastin. In the following decade, multiple other chemical agents were researched for their pro- or anti-ferroptotic properties. Complex organic structures with numerous aromatic moieties make up the majority of this list. This review fills a more overlooked niche by gathering, outlining and setting out conclusions regarding less prominent cases of ferroptosis induced by bioinorganic compounds and reported on within the last few years. The article contains a short summary of the application of bioinorganic chemicals based on gallium, several chalcogens, transition metals and elements known as human toxicants used for the purpose of evoking ferroptotic cell death in vitro or in vivo. These are used in the form of free ions, salts, chelates, gaseous and solid oxides or nanoparticles. Knowledge of how exactly these modulators promote or inhibit ferroptosis could be beneficial in the context of future therapies aimed against cancer or neurodegenerative diseases, respectively.

Identification of EGFR as an essential regulator in chondrocytes ferroptosis of osteoarthritis using bioinformatics, in vivo, and in vitro study

“…Erastin is one of the commonly used inducer of ferroptosis [ 18 ]. The chemical structure of erastin is shown in Fig.…”

Ferroptosis-Based Therapeutic Strategies toward Precision Medicine for Cancer

“…The redevelopment of conventional anticancer drugs and the repurposing of anti-inflammatory, anti-infectious, or antidiabetic agents into ferroptotic therapy have garnered considerable attention in recent years. Bioinorganic compounds, complexes, and nanoparticles can also serve as pro- or antiferroptotic modulators, and some of them are more readily accessible or easier to mass production than organic molecules and extracts . More recently, a proteolysis targeting chimera (PROTAC)-based GPX4 degrader has been established to regulate ferroptosis in vivo.…”

“…Bioinorganic compounds, complexes, and nanoparticles can also serve as proor antiferroptotic modulators, and some of them are more readily accessible or easier to mass production than organic molecules and extracts. 236 More recently, a proteolysis targeting chimera (PROTAC)-based GPX4 degrader has been established to regulate ferroptosis in vivo. The potency of the PROTAC degrader was 5-fold higher than that of the conventional GPX4 inhibitor ML162, and by incorporation into lipid nanoparticles, the degrader exhibited enhanced biocompatibility and tumor inhibitory effect with negligible side effects.…”