Identifying Irg1 inhibitors to modulate macrophage function

National Center For Advancing Translational Sciences

Investigators

Abstract

"This project seeks to identify and develop small molecules that target cis-aconitate decarboxylase (Irg1, Acod1). Irg1 converts cis-aconitate (produced in the TCA cycle) into itaconate, a metabolite that has important roles in inflammatory pathways in macrophage cells. Irg1 expression and activity are elevated during M1-type polarization, resulting in increased intracellular and extracellular itaconate levels. Small molecule inhibitors of Irg1 can be used as tool molecules to further characterize the role of this enzyme in immune cells and develop compounds with therapeutic potential. During this period, the collaborative project team has explored potential high-throughput amenable assays to detect itaconate levels from cellular samples.