Targeting cancer metabolism to develop human lactate dehydrogenase (hLDH)5 inhibitors

[Display omitted] •Development of hLDH5 inhibitors targeting cancer metabolism is described.•Structural information of hLDH5 is summarized for rational anticancer drug design.•Targeting the adenosine and pyruvate/nicotinamide binding pocket is the most promising strategy for the development of hLDH5 inhibitors. Cancer cells feature a switch in glucose metabolism from oxidative phosphorylation to cytoplasm-based glycolysis. This altered cellular metabolic pathway meets the survival and proliferation needs for tumor progression. Targeting the metabolic remodeling could offer opportunities for developing effective anticancer therapeutics. Human lactate dehydrogenase (hLDH)5 plays a crucial part in the promotion of glycolysis and is overexpressed in various human tumors, and thus could be a potential anticancer drug target. Here, we briefly discuss the roles of hLDH5 and its connections with cancer metabolism. Then, we review the reported small molecules in light of their binding modes to hLDH5. Finally, possible directions for future development of hLDH5 inhibitors are proposed. We hope that this review will provoke interest in developing hLDH5 inhibitors.