使用基于时间解析的寡核酸的药物查平台,重新将固糖酸作为抗前列腺癌的 uracil DNA glycosylase 抑制剂
Sang-Cuo Nao1, Le-Sheng Huang1, Daniel Shiu-Hin Chan2
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
Bioorganic chemistry
|February 8, 2024
概括
药物重定向通过时间解析光谱加速,克服了高通量查中的光问题. 固醇被确定为 uracil-DNA glycosylase (UDG) 的强有力的抑制剂,显示出癌症治疗的前景.
科学领域:
- 药物发现和开发 药物发现和开发
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 药物重新定位为传统药物发现提供了更快,更便宜的替代方案.
- 药物化合物的固有光会导致高通量查 (HTS) 中的测试干扰.
- 时间解决技术正在成为克服光相关查挑战的解决方案.
研究的目的:
- 开发一个快速高效的选平台,使用时间解析的辐射光谱.
- 为了识别DNA修复酶, uracil-DNA glycosylase (UDG) 的抑制剂.
- 评估已确定化合物在癌症治疗中的潜力.
主要方法:
- 开发一个基于时间分辨率辐射光谱的选平台.
- 对1456种FDA/EMA批准的药物进行了针对 uracil-DNA glycosylase (UDG) 的查.
- 对已识别的抑制剂对抗5甲抗性癌细胞的协同细胞毒性的评估.
主要成果:
- 固糖酸被确定为 uracil-DNA glycosylase (UDG) 的一个强有力的抑制剂.
- 这种化合物表现出对抗5-甲抗性癌细胞的协同细胞毒性.
- 开发的平台成功地从多样化的药物库中识别出一种生物活性化合物.
结论:
- 时间分辨率辐射光谱为识别生物活性化合物提供了可行的HTS方法,即使是具有固有的光的生物活性化合物.
- 固醇是癌症治疗中进一步研究的有希望的候选人,特别是对于耐药细胞系.
- 这项技术可以探索以前被忽视的药物支架,以寻找治疗潜力.
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