一个mTOR抑制剂发现系统使用药物敏感酵母
Anna K Breen1, Sarah Thomas1, David Beckett1
1Department of Biomedical Sciences, Western University of Health Sciences, Lebanon, OR, 97355, USA.
GeroScience
|January 30, 2025
概括
研究人员开发了一种对药物敏感的酵母菌株,以识别新的TOR抑制剂. 该平台显著提高了针对TOR途径的化合物的检测灵敏度,有助于发现潜在的老年保护和抗癌剂.
科学领域:
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
- 酵母遗传学 酵母遗传学
背景情况:
- 拉帕素 (TOR) 途径的标调节细胞生长和衰老.
- 拉巴胺延长了寿命,但有副作用,需要新的TOR抑制剂.
- 酵母模型为研究TOR和识别抑制剂提供了一个可操作的系统.
研究的目的:
- 开发一种高度敏感的基于酵母的平台,用于识别新型TOR抑制剂.
- 为了提高已知的TOR抑制剂的检测灵敏度.
- 选化合物的TOR通路抑制活性.
主要方法:
- 产生了一组Saccharomyces cerevisiae菌株的面板,其中TOR通路基因发生了突变,并删除了药物排泄基因.
- 创建了一个对药物敏感的酵母背景,以增强抑制剂检测.
- 测试已知的TOR抑制剂 (Torin1,GSK2126458,AZD8055) 和选其他化合物用于TOR1依赖的增长抑制.
主要成果:
- 对药物敏感的酵母系统对Torin1和GSK2126458.8的敏感性增加了200-250倍.
- 通过AZD8055确定了TOR1依赖的生长抑制,这种抑制在野生类型酵母中没有观察到.
- 发现阿米诺菲林是一种新的TOR1依赖生长抑制剂,并没有发现其他几个测试化合物的TOR抑制.
结论:
- 开发的药物敏感酵母平台对于识别TOR路径抑制剂非常有效.
- 该系统为药物发现提供了一个快速,经济高效和敏感的工具.
- 该平台有可能加速识别新的老年保护剂和抗癌剂.
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