使用硫(VI) 化物交换弹头共价药物发现
Huang Huang1,2, Lyn H Jones1,2
1Center for Protein Degradation, Dana-Farber Cancer Institute, Boston, MA, USA.
Expert opinion on drug discovery
|May 27, 2023
概括
硫 (VI) 化物交换 (SuFEx) 化学扩大了对性药物发现的范围. 这种方法可以准多种不同的氨基酸,为新的共价药物候选药物铺平了道路.
科学领域:
- 药用化学 医学化学
- 化学生物学 化学生物学
- 药物发现 药物发现 药物发现
背景情况:
- 传统的共价药物发现主要向氨酸残留物.
- 在蛋白质结合部位中经常缺少氨酸,这限制了共价药物的作用范围.
- 硫 (VI) 化物交换 (SuFEx) 化学提供了对共价变化的新方法.
研究的目的:
- 审查SuFEx药物化学和化学生物学近期的进展.
- 突出SuFEx化学在扩大可药物蛋白质组超出氨酸之外的潜力.
- 讨论开发针对各种氨基酸残留物的共价化学探针.
主要方法:
- 在共价药物设计中探索SuFEx化学.
- 开发选择性共价探针,以准类型的氨基酸,如氨酸,氨酸,氨酸,氨酸,氨酸和氨酸.
- 化学蛋白质组测绘,基于结构的设计和合成方法的应用.
主要成果:
- SuFEx的化学特性使得开发共价探针能够针对更广泛的氨基酸.
- SuFEx的进步促进了化学蛋白质组测绘和基于结构的抑制剂和分子的设计.
- 新的合成方法已经加速了SuFEx调制器的交付.
结论:
- SuFEx化学显著扩大可药物蛋白质组,用于共价药物发现.
- 需要进一步的临床前研究来将SuFEx的创新转化为临床候选药物.
- 预计使用超出氨酸的SuFEx弹头的共价药物候选药物将进入临床试验.
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