通过基于酶合反应的高通量选试验发现了阿尔多酶A抑制剂
Qingwen Xiong1, Rongyu Qian1, Qingcheng Huang2
1School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia, Nanjing 210023, Jiangsu, China; The Center for Chemical Biology, Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Bioorganic & medicinal chemistry letters
|July 12, 2025
概括
研究人员确定了两种潜在的癌症药物化合物 - - 墨胺和基酸 - - 抑制阿尔多酶A (ALDOA). 这种酶是这种酶.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 癌症生物学 癌症生物学
背景情况:
- 阿尔多酶A (ALDOA) 是糖解中的一个关键酶.
- 异常的ALDOA过度表达与各种固体瘤有关.
研究的目的:
- 为ALDOA抑制剂开发一种成本效益高的高通量选 (HTS) 试验.
- 从化合物库中识别新型ALDOA抑制剂.
主要方法:
- 开发了一种用于ALDOA抑制的体外酶合反应试验.
- 通过使用开发的测试,选了公司内部的复合库.
- 使用NMR,SPR和酶动力学验证的抑制剂候选者.
主要成果:
- 确定了和酸作为潜在的ALDOA抑制剂.
- 墨胺和酸的IC50值分别为8.49 ± 0.62 μM和19.87 ± 2.03 μM.
- 核磁共振和SPR证实了高结合亲和度 (Kd:0.49 ± 0.10 μM和0.64 ± 0.10 μM). 核磁共振和SPR证实了高结合亲和度 (Kd:0.49 ± 0.10 μM和0.64 ± 0.10 μM).
- 这两种化合物都作为ALDOA.非竞争性抑制剂.
结论:
- 开发的酶定量对ALDOA抑制剂查有效.
- 墨胺和基酸是ALDOA向癌症治疗的有希望的候选者.
- 这项研究为发现针对ALDOA的新抗癌剂提供了一个有价值的平台.
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