Inhibitors of lactic acid transporter MCT4

描述（由申请人提供）：大多数癌细胞高度糖酵解，即使有足够的氧气进行氧化代谢，也会将葡萄糖代谢为乳酸，这种现象称为瓦尔堡效应。已显示瓦尔堡效应促进肿瘤生长、使存活成为可能并刺激转移。 在该项目中，我们描述了一种通过抑制MCT 4直接拮抗癌细胞中的瓦尔堡效应的策略，MCT 4是一种乳酸输出蛋白，是瓦尔堡效应所需的，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小分子MCT4抑制剂。在这个项目中，我们将使用这种化合物来验证MCT 4作为癌症靶点，使用体外和体内方法。我们还将开发更有效的MCT 4抑制剂，最终目标是在临床试验中评估MCT 4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