Abstract 1744 Inhibitors of cytosolic Malate Dehydrogenase mediate selective cytotoxicity against Triple Negative Breast Cancer

Malate dehydrogenases (MDH) are metabolic enzymes involved in catalyzing the reversible conversion of malate to oxaloacetate in the presence of the electron carrier NAD+/NADH. Both MDH isoforms found in humans play crucial roles in maintaining cellular metabolic homeostasis either through the malate-aspartate shuttle or the citric acid cycle. While the cytoplasmic MDH (MDH-1) favors the NADH and oxaloacetate reaction crucial for the malate-aspartate shuttle, mitochondrial MDH (MDH-2) favors the NAD+ and the malate side of the reaction pivotal in the citric acid cycle.