ERG344

ERG344 is a small molecule inhibitor of Immune Responsive Gene 1 (IRG1), also known as Aconitate Decarboxylase 1 (ACOD1), developed by Ergon Pharmaceuticals. IRG1 is an enzyme expressed in macrophages and certain cancer cells that catalyzes the production of itaconate from cis-aconitate. Itaconate acts as an immunosuppressive metabolite in the tumor microenvironment, promoting tumor growth by modulating myeloid-derived suppressor cells (MDSCs) and inhibiting T-cell activity. By blocking IRG1, ERG344 reduces itaconate levels, leading to a decrease in monocytic MDSCs and an increase in the frequency and activity of cytotoxic CD8+ T cells. Preclinical studies have demonstrated that ERG344, administered either orally or intraperitoneally, suppresses tumor growth and improves survival in syngeneic models of colon cancer and melanoma.