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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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人工智能驱动的新型p53-Y220C反应器的发现
Shan Zhou1, Dafei Chai1, Xu Wang1
1Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, United States.
Frontiers in oncology
|August 18, 2023
概括
人工智能识别了化合物H3,该化合物在p53-Y220C突变中恢复了野生类型的p53形状. 这种化合物可以选择性地杀死癌细胞,并抑制小鼠的瘤生长.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- p53-Y220C突变是癌症进展的常见驱动因素.
- 恢复野生型p53功能是这种突变癌症的治疗策略.
研究的目的:
- 在p53-Y220C突变体中识别小分子化合物,以恢复野生类型的p53构造.
- 在临床前癌症模型中评估已识别化合物的疗效.
主要方法:
- 用人工智能 (AI) 驱动的1000万种化合物的虚拟选.
- 使用具有各种p53突变的细胞系进行实验验证.
- 在老鼠异种移植模型中的体内疗效评估.
主要成果:
- 人工智能发现了83种高得分的化合物,其中H3对p53-Y220C突变细胞具有优先活性.
- 化合物H3恢复了野生类型的p53形状和转录活性.
- 在小鼠中,H3诱导细胞循环停止,细胞亡和减少瘤生长.
结论:
- 人工智能有助于发现H3,一种选择性的p53-Y220C反应激活剂.
- 在p53-Y220C驱动的癌症中,H3显示出抑制瘤发展的治疗潜力.
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