遗传病死途径的小分子调节剂:药物化学的视角
De-Chang Li1, Nan-Nan Chen1, Qi-Dong You1
1State Key Laboratory of Natural Medicines, Jiang Su Key Laboratory of Drug Design & Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
European journal of medicinal chemistry
|February 3, 2026
概括
死细胞亡是一种受调节的细胞死亡途径,与各种疾病有关. 本综述详细介绍了针对RIPK1,RIPK3和MLKL的小分子调节剂,以及对炎症状况的临床试验中的一些抑制剂.
科学领域:
- 生物化学和分子生物学
- 药理学和药物发现
- 免疫学 免疫学 免疫学
背景情况:
- 亡是一种涉及RIPK1/RIPK3/MLKL的编程亡途径,有助于神经退行,炎症和癌症等疾病.
- 开发针对性治疗死细胞灭绝的方法对于治疗这些多样化的病态至关重要.
研究的目的:
- 综合审查开发亡途径小分子调节器的进展情况.
- 详细说明RIPK1,RIPK3和MLKL抑制剂和诱导剂的分类,机制和结构-活性关系 (SAR).
主要方法:
- 对小分子调节器的系统性文献综述,以杀死途径组件为目标.
- 对药物开发史的分析,包括临床试验状态和挑战.
- 探索新兴策略,如多目标抑制剂,双功能分子和人工智能驱动的药物设计.
主要成果:
- 一些RIPK1抑制剂已经进入了多发性硬化症和类风湿性关节炎等疾病的II期临床试验.
- 该综述对各种RIPK1,RIPK3和MLKL抑制剂和诱导剂的SAR进行了分类和详细说明.
- 讨论了诸如多目标抑制剂和人工智能驱动的设计等新兴方法.
结论:
- 在开发亡途径调节器方面取得了重大进展.
- 在化学支架设计,减轻目标外影响和改善血脑屏障透方面仍然存在挑战.
- 这一综述为未来针对死的药物发现研究提供了基础.
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