Identification of the mechanism of action of CYT-0851, an inhibitor of monocarboxylate transporter (MCT) mediated lactate transport

CYT-0851 was discovered using a phenotypic screen and rapidly advanced to a phase 1 clinical trial where responses in solid tumor and lymphoma patients have been observed. To elucidate the mechanism of action (MOA) of CYT-0851, extensive bioinformatic, functional genomic, and molecular characterization was performed. This preclinical work demonstrated that CYT-0851 disrupts lactate transport via inhibition of monocarboxylate transporter (MCT) activity. In rapidly proliferating cancers, lactate is produced during glycolysis and is exported primarily by MCT1 and MCT4, which provide functional redundancy when co-expressed.