农业化学品作为ATTRv氨基粉症抑制剂的重新用途
Takeshi Yokoyama1, Satoru Fujiwara2, Kai Nishikubo3
1Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0914, Japan.
Journal of medicinal chemistry
|January 6, 2025
概括
研究人员选了农药化合物,以寻找对跨氨基粉症 (ATTRv) 的新疗法. 氧尼尔和氧尼尔在抑制粉样蛋白纤维素形成方面表现有前途,提供了潜在的治疗途径.
科学领域:
- 药用化学 医学化学
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
背景情况:
- ATTRv氨基粉症是由于TTR错误折叠成氨基粉纤维造成的,导致器官损伤.
- 动力稳定TTR是ATTRv氨基粉症的关键治疗策略.
- 识别新型TTR稳定化合物对于开发有效治疗方法至关重要.
研究的目的:
- 从农药相关分子图书馆中识别ATTRv氨基粉症的潜在治疗化合物.
- 评估选定化合物的结合和动力稳定TTR的能力.
- 评估已识别的化合物在抑制TTR粉样纤维素形成方面的有效性.
主要方法:
- 在651种农药相关化合物的in silico选中,以确定潜在的TTR结合剂.
- 在体外测试以评估候选化合物的粉样纤维素形成抑制活性.
- 对有前途的化合物进行干效率和选择性TTR结合的评估.
主要成果:
- 从最初的查中,有14种化合物被确定为潜在的TTR结合剂.
- 7种化合物在体外表现出粉样纤维素形成抑制活性.
- 氧尼尔和氧尼尔表现出高的连接剂效率和强大的抑制V30M-TTR粉样蛋白纤维的形成.
- 阿克洛尼芬显示中度抑制和选择性TTR结合,与tafamidis.com相比.
结论:
- 农药衍生化合物,包括氧尼尔和氧尼尔,是ATTRv氨基粉症治疗药物的有希望的主要候选者.
- 进一步优化选择性TTR结合和纤维细胞形成抑制是有必要的.
- 这项研究突出了利用现有化学图书馆的潜力,以在amyloidosis中发现新药.
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