Monocarboxylate transporter (MCT) (MCT)

Monocarboxylate transporters (MCTs) are a family of 14 transmembrane proteins, encoded by the SLC16 gene family, that facilitate the proton-coupled transport of monocarboxylates such as lactate, pyruvate, and ketone bodies across cell membranes [1, 4]. They play a critical role in maintaining cellular pH and metabolic homeostasis, particularly in tissues with high glycolytic rates like skeletal muscle and the brain [3, 6]. In the context of oncology, MCT1 and MCT4 are frequently overexpressed to support the "Warburg effect," allowing cancer cells to export excess lactic acid and avoid intracellular acidification [2, 10]. Therapeutic strategies focus on inhibiting these transporters to disrupt cancer metabolism, with drugs like AZD3965 (MCT1 inhibitor) and AZD0095 (MCT4 inhibitor) undergoing clinical and preclinical evaluation [13, 15]. However, targeting MCTs presents challenges, including potential retinal toxicity due to the high expression of MCT1 and MCT3 in the eye, and metabolic compensation where cells upregulate alternative isoforms to survive [12, 21]. Beyond cancer, mutations in specific family members like MCT8 are linked to severe neurological disorders such as Allan-Herndon-Dudley syndrome [4, 9]. Additionally, MCT1 has been utilized in drug delivery to enhance the absorption of prodrugs like gabapentin enacarbil in the intestine [2, 4].

Other names

Solute carrier family 16SLC16 familyProton-linked monocarboxylate transporterLactate transporter

Inhibition of monocarboxylate (primarily lactate) efflux or influx, leading to intracellular acidification, metabolic stress, and disruption of the Warburg effect in cancer cells.