Itaconic acid 4-octyl ester [4-Octyl itaconate]
40 CHF CHF 40.00
AG-CR1-3700-M01010 mgCHF 40.00
AG-CR1-3700-M05050 mgCHF 90.00
|Synonyms||4-Octyl ester 2-methylene-butanedioic acid; 4-Octyl methylenesuccinate; β-Monooctyl itaconate|
|Purity Chemicals||≥98% (mixture of tautomers)|
|Solubility||Soluble in DMSO (30mg/ml), ethanol (30mg/ml) or DMF (30mg/ml).|
|Shipping and Handling|
|Short Term Storage||+4°C|
|Long Term Storage||-20°C|
|Handling Advice||Keep cool and dry.|
|Use/Stability||Stable for at least 2 years after receipt when stored at -20°C.|
|Product Specification Sheet|
- Derivative of itaconate (AG-CN2-0426) with enhanced cell permeability. Prodrug that is efficiently metabolized to itaconate in cells.
- Potent anti-inflammatory agent.
- In vitro it activates the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) (also known as NFE2L2) in LPS-induced mouse and human macrophages.
- Upregulates Nrf2 levels via a newly identified post-translational modification, dicarboxylation of KEAP1. Alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream gene. Cysteine 151 is uniquely required for inhibiting KEAP1-mediated degradation of Nrf2 and mutating this residue in KEAP1 prevents the stabilization of Nrf2.
- LPS induces itaconate production, partly via the induction of type I IFNs; this results in Nrf2 stabilization (via itaconate-mediated cysteine alkylation of KEAP1) that promotes an anti-inflammatory response, which is accompanied by the downregulation of itaconate production through reduced IFN expression.
- In vivo (50 mg/kg) it decreases serum levels of IL-1β and TNF-α, increases Nrf2 protein expression and protects against LPS-induced lethality in wild-type, but not Nrf2 knockout mice.
- Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1: E.L. Mills, et al.; Nature 556, 113 (2018)