一个独特的类别的二甲氨酸和CC-1065类似物受减小激活
Wei Jin1, John D Trzupek, Thomas J Rayl
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|November 21, 2007
概括
新的抗瘤前药在缺氧瘤中被激活,有效释放活性药物. 这些新型药物在体内表现出强大且增强的疗效,为向癌症治疗提供了优势.
科学领域:
- 药用化学 医学化学
- 癌症药理学 癌症药理学
- 药物开发 药物开发
背景情况:
- 杜阿卡米辛和CC-1065是强大的抗瘤剂.
- 低毒瘤环境具有更高的减少能力.
- 降低活性激活为有针对性的药物输送提供了一种策略.
研究的目的:
- 开发和描述杜卡米和CC-1065.5的新型减少活性前药物.
- 评估这些前药物的稳定性和释放动力学.
- 评估前药物的体外和体内疗效.
主要方法:
- 合成N-乙O-氨基衍生物.
- 在癌症细胞系中的体外细胞毒性测定.
- 在体外DNA化和稳定性研究.
- 在动物模型中进行的体内疗效研究.
主要成果:
- 代药在细胞测定中显示出有效的药物释放和细胞毒性活性.
- 前代药在生理条件下在体外表现出稳定性.
- 在体内研究表明,前药物与免费药物的疗效相匹配或超过.
结论:
- N-acyl O-amino 衍生物代表了一种新的降解活性前药物类.
- 这些前期药物具有针对性癌症治疗的潜力,具有增强的疗效.
- 这些前药物在体内应用时表现出有利的稳定性和释放特征.
相关概念视频
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