Inhibitors of lactic acid transporter MCT4

描述(申请人提供)：大多数癌细胞是高度糖酵解的，即使有足够的氧气进行氧化代谢，也能将葡萄糖代谢成乳酸，这种现象被称为Warburg效应。华宝效应已被证明可以促进肿瘤生长，使患者存活，并刺激转移。在这个项目中，我们描述了一种通过抑制MCT4在癌细胞中直接对抗Warburg效应的策略，MCT4是一种乳酸输出物，是Warburg效应所必需的，在许多癌症适应症中高度上调。我们发现了一种有效的、选择性的MCT4小分子抑制剂。在这个项目中，我们将使用这种化合物来验证MCT4作为癌症靶点的有效性，使用体外和体内的方法。我们还将开发更有效的MCT4抑制剂，最终目标是在临床试验中评估MCT4抑制作用。1

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 vivo approaches. We will also develop more potent MCT4 inhibitors with the ultimate goal of evaluating MCT4 inhibition in clinical trials. 1