Monocarboxylate transporter 1 and 2 (MCT1/2)

Monocarboxylate transporter 1 (MCT1) and 2 (MCT2) are members of the solute carrier family 16 (encoded by SLC16A1 and SLC16A7, respectively) that facilitate the proton-coupled, bidirectional transport of monocarboxylates such as lactate, pyruvate, and ketone bodies across cell membranes [UniProt, Wikipedia]. These transporters are vital for maintaining metabolic homeostasis and intracellular pH, particularly through the 'lactate shuttle' where lactate produced by glycolytic cells is exported and subsequently taken up by oxidative cells as a respiratory fuel [PubMed, NIH]. In the context of oncology, many tumors overexpress MCT1 and MCT2 to sustain high rates of glycolysis (the Warburg effect) by exporting excess lactate to prevent lethal intracellular acidification, while oxidative tumor cells may use them to import lactate as a primary fuel source [GeneCards, PubMed]. Consequently, MCT1/2 are significant therapeutic targets, with inhibitors like AZD3965 being developed to disrupt tumor energy metabolism and the immunosuppressive acidic microenvironment [ClinicalTrials.gov]. However, the efficacy of MCT1 inhibition can be limited by the compensatory expression of MCT4, and clinical use is challenged by on-target toxicities in the retina and heart, where MCT1 is physiologically essential [NIH, PubMed]. Additionally, mutations or aberrant expression of these transporters are linked to metabolic disorders such as hyperinsulinemic hypoglycemia and ketoacidosis [Wikipedia, UniProt].

Other names

SLC16A1SLC16A7Monocarboxylate transporter 1Monocarboxylate transporter 2Solute carrier family 16 member 1Solute carrier family 16 member 7MCT1MCT2HHF7MCT1D

Inhibition of bidirectional proton-coupled monocarboxylate transport, leading to intracellular acidification, disruption of glycolytic metabolism, and inhibition of lactate-mediated metabolic symbiosis.