Recent developments of human monocarboxylate transporter (hMCT) inhibitors as anticancer agents

•Recent development of hMCTs inhibitors targeting cancer metabolism is described.•Structural information of hMCT1 and hMCT4 is summarized for rational anticancer drug design.•Future directions for the development of hMCTs inhibitors are highlighted. Cancer cells metabolize glucose via anaerobic glycolysis, with lactate formed in the cytosol as the end-product. To avoid intercellular acidification, excessive lactate and proton are excreted by monocarboxylate transporters (MCTs), which are often overexpressed in different malignant cancers. Targeting the MCT-mediated lactate/proton efflux makes MCTs a potentially interesting anticancer target. Although X-ray co-crystal structures of human MCTs with inhibitors are not yet available, homology models have been established, which helped to rationalize the binding modes and the design of new MCT inhibitors. In this review, we discuss the structures and functions of MCTs as well as recently reported small-molecule MCTs inhibitors. We assess the current development of MCT inhibitors and highlight possible directions for future development.