在表观遗传疗法中降解剂:PROTACs和超越
Xing-Jie Dai1, Shi-Kun Ji1, Meng-Jie Fu1
1Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment; Key Laboratory of Henan Province for Drug Quality and Evaluation; Institute of Drug Discovery and Development; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Theranostics
|February 23, 2024
概括
向蛋白降解 (TPD) 提供了针对癌症治疗的表观遗传蛋白的新方法. 本综述探讨了超越PROTACs的小分子降解剂,强调了它们的潜力和挑战.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 表观遗传学影响基因表达而不改变DNA序列,使其成为治疗癌症等疾病的关键目标.
- 现有的表观遗传药物面临的局限性包括狭窄的适用性,毒性和耐药性.
- 包括PROTAC在内的向蛋白降解 (TPD) 策略已取得显著进展.
研究的目的:
- 对表观遗传蛋白质标的小分子降解剂进行审查,超越PROTACs.
- 通过蛋白质体或溶酶体路径探索降解机制.
- 讨论在开发表观遗传药物的当前挑战和未来前景.
主要方法:
- 针对针对表观遗传蛋白质的小分子降解剂的综合文献综述.
- 除了PROTAC之外的各种TPD策略的分析 (例如分子,dTAG).
- 对表观遗传点的蛋白质和溶酶体降解途径的检查.
主要成果:
- 小分子降解剂提供了针对表观遗传蛋白的替代方法,包括代蛋白,基因素乙化/脱乙化和甲基化点.
- 这些降解剂利用蛋白质或 lysosomal 途径去除蛋白质.
- 该审查强调了除了PROTAC之外的各种TPD策略.
结论:
- 小分子降解剂代表了开发新型表观遗传疗法的有希望的前沿.
- 克服强度,选择性和药物相似性的挑战对于临床翻译至关重要.
- 对TPD机制的进一步研究可以导致更有效的表观遗传药物.
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