GNE-140 is an orally active and selective inhibitor of lactate dehydrogenase (LDH) A, B and C, with IC50 values of 3, 5 and 5 nM against LDHA, LDHB, LDHC, respectively. GNE-140 blocks the conversion of pyruvate to lactate, reduces lactate production and histone lysine lactylation, and inhibits glycolysis. GNE-140 attenuates cardiac hypertrophy, alleviates PM2.5-induced pulmonary inflammation and fibrosis, blocks MRSA-induced Arg1 expression, regulates metabolites of glycolysis and the pentose phosphate pathway, reduces glucose uptake, increases ROS, and induces cancer cell apoptosis. GNE-140 is applicable to research related to pathological cardiac hypertrophy, pulmonary fibrosis, MRSA infection and pancreatic cancer.
