4-Octyl Itaconate, a cell-permeable derivative of Itaconate, is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1 and inhibits phosphorylation of STING.

METHODS: Human PBMC cells were pretreated with 4-Octyl Itaconate (62.5-125 μM) for 3 h. The expression levels of target proteins were detected by Western Blot.
RESULTS: 4-Octyl Itaconate decreased LPS-induced pro-IL-1β and HIF-1α protein levels. [1]
METHODS: Macrophage THP1 cells were treated with 4-Octyl Itaconate (200 ng/mL) for 2 h, then stimulated with 2′,3′cGAMP for 1 h. The level of p-STING was detected by Immunofluorescence.
RESULTS: 4-Octyl Itaconate pretreatment resulted in a significant inhibition of STING phosphorylation. [2]

METHODS: To test the anti-inflammatory activity in vivo, 4-Octyl Itaconate (50 mg/kg in 40% cyclodextrin in PBS) was intraperitoneally injected into mice, and 2 h later LPS (2.5 mg/kg) was intraperitoneally injected.
RESULTS: 4-Octyl Itaconate counteracted the pro-inflammatory response to LPS in vivo. 4-Octyl Itaconate activated Nrf2, prolonged survival, decreased clinical scores and improved thermoregulation, and decreased IL-1β and TNF levels, but not IL-10, in the LPS model of sepsis. [1]
METHODS: To investigate the role in immunosuppressive impairment in sepsis, 4-Octyl Itaconate (25-50 mg/kg) was injected intraperitoneally into a C57bl/6 mouse model of sepsis established by cecum ligation and puncture (CLP).
RESULTS: 4-Octyl Itaconate inhibits the early release of inflammatory and oxidative stress-related factors to reduce tissue and organ damage in septic mice. [3]