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

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.

Automated summary

MCTs play a crucial role in lactate/proton efflux and may serve as a new target for anticancer therapies. While X-ray co-crystal structures of human MCTs with inhibitors are unavailable, homology models have aided in the design of new MCT inhibitors. Future directions include studying the structures and functions of MCT inhibitors and discovering more small-molecule inhibitors.