dimethyl itaconate   Click here for help

GtoPdb Ligand ID: 9939

Synonyms: dimethylitaconate | itaconic acid dimethyl ester
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Dimethyl itaconate is a membrane-permeable derivative of the immunoregulatory metabolite itaconate. Itaconate is one of the most highly induced metabolites produced when activated macrophages undergo metabolic remodeling. Itaconate acts as a major physiological regulator of metabolic switching and effector functions of inflammatory macrophages. Itaconate and dimethyl itaconate inhibit production of IL-6 and IL-12 (secondary transcriptional response), but not TNF (a primary transcriptional response) following Toll-like receptor stimulation [4].

Itaconate has been found to promote an electrophilic stress response (i.e. a rapid adaptive defense response) [1]. An electrophilic stress response involves various mechanisms, including the nuclear translocation of the redox-sensitive transcription factor Nrf2 (nuclear factor E2-related factor 2), which senses electrophilic and oxidative stresses and protects against cellular damage via Kelch-like ECH-associated protein 1 (Keap1) [2-3,5]. Both itaconate and dimethyl itaconate induce Nrf2-dependent and -independent responses, the Nrf2-independent response being that which involves regulation of IκBζ [1].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 0
Rotatable bonds 5
Topological polar surface area 52.6
Molecular weight 158.06
XLogP 0.24
No. Lipinski's rules broken 0
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Canonical SMILES COC(=O)CC(=C)C(=O)OC
Isomeric SMILES COC(=O)CC(=C)C(=O)OC
InChI InChI=1S/C7H10O4/c1-5(7(9)11-3)4-6(8)10-2/h1,4H2,2-3H3
No information available.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Dimethyl itaconate is reported to induce electrophilic stress, which ultimately leads to down-regulation of secondary (but not primary) transcriptional responses to Toll-like receptor stimulation. The dimethyl itaconate effect inhibits up-regulation of transcription of the NF-κB transcriptional regulator, IκBζ [1].