部署高通量虚拟查 (HTVS) 方法,用于识别具有抗癌活性的新型乳酸脱酶 (LDH) 抑制剂
Yaxun Huang1,2, Sangeeta Benni3, Umesh Prasad Yadav4
1Department of Liver Transplantation, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Scientific reports
|January 21, 2026
概括
研究人员确定了新型化合物来抑制乳酸脱酶 (LDH),这是一种对癌细胞存活和瘤微环境至关重要的酶. 这一发现为癌症治疗提供了潜在的新疗法策略.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 药物发现 药物发现 药物发现
背景情况:
- 瘤细胞经常利用氧化化 (沃伯格效应) 的糖解来产生ATP.
- 乳酸脱酶 (LDH) 将酸盐转化为乳酸盐,为瘤微环境提供燃料,并补充NAD+用于糖解.
- 在癌细胞预后,生存和调节瘤微环境方面,LDH起着至关重要的作用.
研究的目的:
- 通过高通量虚拟选方法识别抑制乳酸脱酶 (LDH) 活性的新型化合物.
- 解决目前批准用于癌症治疗的LDH抑制剂的缺口.
主要方法:
- 基于28个已知的LDH抑制剂生成了一个药科孔模型.
- 使用药模型选了50万个配体,随后进行了分子对接和药物相似性过.
- 针对已识别的命中物进行了分子动力学 (MD) 模拟,并对所选化合物进行了生物验证 (15和422联结物).
主要成果:
- 在虚拟选和过后,确定了5个潜在的打击化合物.
- 选择的体15和422表现出显著的LDH抑制,其IC50值分别为147.34nM和206.35nM.
- 这两种化合物都在DU-145和PC-3细胞系中表现出抗癌特性,诱导细胞亡并改变线粒体功能.
结论:
- 已识别的化合物 (配体15和422) 显示出作为具有抗癌潜力的新型LDH抑制剂的前景.
- 这些发现有助于开发针对癌症中LDH的新治疗策略.
- 需要进一步的研究和临床试验来探索这些化合物的治疗疗效.
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