4-octyl Itaconate

4-octyl Itaconate is a prodrug form of itaconate, an endogenous cellular metabolite produced via decarboxylation of cis-aconitate by the enzyme encoded by IRG1.{42667,40962} It is hydrolyzed to itaconate by esterases in C2C12 cells and LPS-activated mouse macrophages where it acts as a regulator of macrophage function with anti-inflammatory properties.{40962} 4-octyl Itaconate increases nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and expression of Nrf2 target genes and enhances LPS-induced Nrf2 stabilization in mouse macrophages. In vivo, 4-octyl itaconate (50 mg/kg) decreases serum levels of IL-1B and TNF-a, increases Nrf2 protein expression, and protects against LPS-induced lethality in wild-type, but not Nrf2 knockout, mice.