MSC-4381

MSC-4381 is a potent and selective small molecule inhibitor of the monocarboxylate transporter 4 (MCT4), also known as **Solute carrier family 16 member 3** (SLC16A3). MCT4 is a key lactate transporter that facilitates the export of lactate from glycolytic cancer cells, a process essential for maintaining intracellular pH and redox homeostasis. By blocking SLC16A3-mediated lactate export, MSC-4381 induces intracellular lactate accumulation, disrupts mitochondrial function, and promotes **ferroptosis**, a form of regulated cell death driven by lipid peroxidation. Research indicates that MSC-4381 can overcome resistance to EGFR tyrosine kinase inhibitors (TKIs) like gefitinib in lung adenocarcinoma (LUAD) by restoring ferroptosis sensitivity. It has demonstrated synergistic efficacy with gefitinib in both in vitro and in vivo xenograft models, supporting its potential as a therapeutic strategy for targeting metabolic vulnerabilities in EGFR-TKI resistant cancers.