Abstract 1878 Uncovering Mechanisms of DGK Inhibition Using a Live-Cell Imaging Platform

Phosphatidic acid (PA) is essential for plasma membrane (PM) function, including membrane bending, enzyme recruitment, and lipid biosynthesis. Disruptions in diacylglycerol kinase (DGK) activity that produces PA is linked to immune dysfunction, oncogenic signaling, and cardiovascular diseases. The ten DGK isoforms are known druggable targets. However, our understanding of the mechanism of inhibition of the DGKs is still limited. This study aimed to characterize how the DGK inhibitors R59022 and BMS-502 interact with the various DGK isoforms and to demonstrate their effectiveness in inhibiting PA production after G-protein coupled receptor (GPCR) stimulation.