Inhibitors of lactic acid transporter MCT4

DESCRIPTION (provided by applicant): Most cancer cells are highly glycolytic, metabolizing glucose to lactic acid even when sufficient oxygen is available to perform oxidative metabolism, a phenomenon known as the Warburg effect. The Warburg effect has been shown to promote tumor growth, enable survival, and stimulate metastasis. In this project, we describe a strategy to directly antagonize the Warburg effect in cancer cells through the inhibition of MCT4, a lactic acid exporter that is required for the Warburg effect and is highly upregulated in many cancer indications. We have discovered a potent and selective small molecule inhibitor of MCT4. In this project, we will use this compound to validate MCT4 as a cancer target, using both in vitro and in vivoapproaches. We will also develop more potent MCT4 inhibitors with the ultimate goal of evaluating MCT4 inhibition in clinical trials. 1 PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Cancer is the leading cause of death in the developed