MCT1

MCT1 (SLC16A1) is a proton-linked monocarboxylate transporter that mediates the bidirectional transmembrane movement of lactate, pyruvate, and ketone bodies, thereby supporting cellular metabolism and pH homeostasis^[1][2]. Mechanistically, MCT1 participates in lactate shuttling between metabolically distinct cell populations and contributes to the maintenance of glycolytic flux through coordinated transport of monocarboxylates and protons^[1][2]. Because lactate transport is a central component of metabolic adaptation, MCT1 has been extensively investigated in cancer models in which lactate exchange supports tumor growth and metabolic plasticity^[3][4]. Inhibition of MCT1 disrupts lactate transport, alters glycolytic metabolite profiles, and suppresses tumor growth in multiple preclinical models^[3][4]. Compared with related isoforms, MCT1 displays distinct substrate and inhibitor affinities, whereas MCT4 is relatively resistant to several widely used MCT1-directed inhibitors, creating important functional differences in lactate-handling networks^[2][5]. This isoform selectivity is particularly relevant for experimental design because cellular responses to MCT1 blockade can depend on the presence or absence of compensatory MCT4 expression^[4][5]. For experimental applications, AZD3965 is a first-in-class MCT1 inhibitor that induces intracellular lactate accumulation and has advanced into clinical evaluation, while AR-C155858 potently inhibits MCT1 and MCT2 through binding determinants located within transmembrane helices 7-10 but shows little activity against MCT4^[4][5].