4-octylitaconic acid

4-octylitaconic acid (also known as 4-octyl itaconate or 4-OI) is a synthetic, cell-permeable ester derivative of the endogenous immunometabolite itaconate. It is widely used as a research-use-only tool compound to investigate the anti-inflammatory, antioxidant, and immunomodulatory properties of itaconate. Intracellularly, 4-octylitaconic acid is hydrolyzed by esterases to release itaconate. It exerts its therapeutic-like effects primarily by covalently alkylating cysteine residues on key proteins. Notably, it alkylates Kelch-like ECH-associated protein 1 (KEAP1), which prevents the degradation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activates the Nrf2 antioxidant response pathway. Additionally, it alkylates and inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), thereby suppressing aerobic glycolysis in macrophages, and alkylates stimulator of interferon genes (STING) to block its activation and downstream type I interferon signaling. It has been studied in preclinical models of sepsis, sepsis-associated encephalopathy, acute lung injury, atopic dermatitis, and other inflammatory conditions.

Other names

4-OI4-octyl itaconate4-octylitaconateitaconic acid 4-octyl esteroctyl itaconateβ-monooctyl itaconate