dimethyl alpha-ketoglutarate

Dimethyl alpha-ketoglutarate (DM-AKG) is a cell-permeable, small-molecule derivative of alpha-ketoglutarate (AKG), a central intermediate in the tricarboxylic acid (TCA) cycle. By incorporating two methyl groups, DM-AKG exhibits significantly enhanced membrane permeability compared to AKG, allowing it to effectively raise intracellular AKG levels. It acts as a multi-target agent, inhibiting matrix metalloproteinases (MMPs) such as MMP-1, MMP-9, MMP-10, and MMP-12, and modulating the autophagy and PINK1/Parkin-mediated mitophagy pathways. Furthermore, it serves as a cofactor for various alpha-ketoglutarate-dependent dioxygenases involved in epigenetic regulation, such as histone demethylases. Preclinical research has investigated its potential in treating acute kidney injury, liver fibrosis, cardiomyopathy, and neurodegenerative diseases like Alzheimer's, as well as its application in oncology for glioblastoma and diffuse intrinsic pontine glioma (DIPG). It is also explored as an anti-wrinkle cosmetic ingredient due to its ability to promote collagen synthesis and inhibit MMPs.

Other names

dimethyl 2-oxoglutaratedimethyl2-oxoglutaratedimethyl-2-oxoglutaratedimethyl 2-oxopentanedioatedimethyl2-oxopentanedioatedimethyl-2-oxopentanedioatedimethyl alpha-ketoglutaric acid