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Lactate dehydrogenase A (LDHA) inhibitors block the enzyme that turns pyruvate into lactate. The reaction regenerates oxidized nicotinamide adenine dinucleotide (NAD+), so glycolysis can continue when mitochondrial oxidation is limited. Many tumor cells rely on this step for aerobic glycolysis, also called the Warburg effect. In 2006, lowering LDHA expression in tumor cells raised mitochondrial respiration and impaired tumor growth. FX-11 was reported in 2010 to induce oxidative stress and slow the growth of lymphoma and pancreatic cancer xenografts. GSK2837808A is a further LDHA inhibitor, and GNE-140 is listed as GNE-140 racemate and as (R)-GNE-140 and (S)-GNE-140. Sodium oxamate, a classic substrate analog, competes with pyruvate at several lactate dehydrogenase isoforms.
LDHA-IN-7 is a potent inhibitor of lactate dehydrogenase-A (LDHA) and lactate dehydrogenase-B (LDHB), with IC50 values of 72 nM and 1.2 μM, respectively. This compound demonstrates impressive oral bioavailability, making it a valuable tool for studying metabolic pathways involving lactate metabolism. LDHA-IN-7 is particularly useful in cancer research and other conditions where lactate dehydrogenase activity is implicated.
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