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AVANTI POLAR LIPIDS , CYGNUS , LARODAN , ADIPOGEN , MYBIOSOURCE , SERVA NORDMARK, BIOWORLD, EDGEBIO , PANREAC APPLICHEM
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Product description: Chemical. CAS: 3133-16-2. Formula: C13H22O4. MW: 242.3. Derivative of itaconate (AG-CN2-0426 https://adipogen.com/ag-cn2-0426-itaconic-acid.html ) 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-1beta and TNF-alpha, increases Nrf2 protein expression and protects against LPS-induced lethality in wild-type, but not Nrf2 knockout mice.
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