GNE-140

GNE-140 is a potent and selective small molecule inhibitor of lactate dehydrogenase A (LDHA), originally developed by Genentech. It functions by blocking the conversion of pyruvate to lactate, a key step in anaerobic glycolysis. In research settings, GNE-140 is widely used as a tool compound to study metabolic reprogramming, particularly the "Warburg effect" in oncology and metabolic shifts in cardiovascular diseases. Recent studies indicate that GNE-140 can protect cardiomyocytes from myocardial ischemia-reperfusion injury (MIRI) by redirecting glucose metabolism toward the pentose phosphate pathway (PPP). This metabolic shift enhances the production of NADPH and ATP while reducing the generation of mitochondrial reactive oxygen species (ROS), ultimately decreasing cardiomyocyte apoptosis and improving long-term cardiac function.