Structure-guided screening identifies Tucatinib as dual inhibitor for MCT1/2

ABSTRACT: Cell surface glycoproteins, Basigin or embigin, associate with proton-coupled monocarboxylate transporters (MCTs) to form heterodimers. These associations enhance MCTs membrane trafficking and modulate their transport functions. Cancer cells often undergo metabolic reprogramming, which increases glycolysis and lactate production. Proton-coupled MCTs are crucial for maintaining this metabolic state by shuttling lactate across membranes, thus aiding in pH regulation within cancer cells. A deeper understanding of MCTs regulation may open avenues for the development of novel inhibitors, potentially applicable in clinical settings. In this study, we determine the cryo-EM structures of the human MCT2-embigin complex in both apo and AR-C155858-bound states, and observe that embigin engages in ext

SUBMITTER: Binghong Xu 

PROVIDER: S-SCDT-10_1038-S44319-025-00661-9 | biostudies-other |

REPOSITORIES: biostudies-other