Identification of a potent inhibitor targeting human lactate dehydrogenase A and its metabolic modulation for cancer cell line

Targeting LDHA represents a promising strategy for the development of new anti-cancer agents. We report herein the identification of a potent compound as a direct LDHA inhibitor. The in vitro enzymatic assay revealed that the VS-2 had good inhibitory potency (IC50 = 0.25 μM) to LDHA. Cytotoxic assay suggested that the VS-2 could inhibit MCF-7 cancer cell growth, with the IC50 value low to 1.54 μM. The seahorse XF24 experiment validated that the VS-2 served as a modulator to reprogram MCF-7 cancer cell metabolism from glycolysis to mitochondrial respiration.

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