作为候选药物的宏环:最近的进展和剩余的挑战
Alexander A Vinogradov1, Yizhen Yin1, Hiroaki Suga1
1Department of Chemistry, Graduate School of Science , The University of Tokyo , 7-3-1 Hongo , Bunkyo-ku, Tokyo 113-0033 , Japan.
Journal of the American Chemical Society
|February 16, 2019
概括
类疗法有前途,但在稳定性和交付方面面临挑战. 这篇评论探讨了诸如宏环化和非原生氨基酸等策略,以增强类药物特性以提高治疗成功.
科学领域:
- 医学化学
- 药物发现
- 生物技术
背景情况:
- 由于合成可访问性和特定结合性,是一种有吸引力的治疗药物.
- 低代谢稳定性和细胞透性限制了类药物的临床成功.
- 针对"无毒"蛋白质表面是疗法的关键优势.
研究的目的:
- 审查改善类药物特性的策略.
- 分析增强药理学的进展和挑战.
- 讨论最佳类药物候选者的相互矛盾考虑.
主要方法:
- 对类药物开发的宏循环化技术的审查.
- 在设计中对非蛋白质氨基酸的结合进行分析.
- 检查结合策略以改善类药物特性.
主要成果:
- 宏循环,非原生氨基酸和结合增强了的代谢稳定性和细胞透性.
- 这些修改可以克服新发现的生物活性的局限性.
- 最近的进展表明改善个体药理特性是可行的.
结论:
- 优化类候选药物需要平衡多种药理性质.
- 相互矛盾的考虑对推进疗法至关重要.
- 战略性修改为药物开发克服固有的限制提供了途径.
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