molecules of the month

The Merck KGaA MCT4 chemical probe, “compound 18n”, is a novel inhibitor of the monocarboxylate transporter MCT4. Large quantities of lactic acid need to be transported out of tumor cells due to their dependence on glucose metabolism, and this transport is mediated by MCTs. Overexpression of MCT4 is a marker for poor prognosis in cancer, and hence it has been considered as an oncology target, though tools to test the hypothesis were lacking. The Merck team found a starting point in a submicromolar hit (600 nM IC50), which was optimized to an in vivo tool compound. Unfortunately, while treatment with the MCT4 tool in combination with an MCT1/2 tool resulted in an increase in tumor lactate concentration, no significant effect on…