最近开发的ATR抑制剂用于癌症治疗
Jiao Wang1, Yuan Quan2, Ying Shen2
1Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, China.
ATAXIA Telangiectasia和Rad3相关的 (ATR) 激酶抑制剂显示出癌症治疗的前景. 本综述详细介绍了自2018年以来的药物化学进展,重点关注下一代药物设计的支架.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药用化学 医学化学
背景情况:
- ATAXIA Telangiectasia和Rad3相关的 (ATR) 激酶对于基因组稳定性和DNA损伤反应至关重要.
- ATR信号失调与癌症的发展,治疗耐药性和神经退行性疾病有关.
- ATR抑制剂是有前途的癌症治疗药物,临床试验中有几个候选药物.
研究的目的:
- 审查自2018年以来ATR抑制剂开发的药物化学进展.
- 系统地分析ATR抑制剂设计中使用的主要化学支架.
- 为开发具有改善临床特征的下一代ATR抑制剂提供指导.
主要方法:
- 文献综述侧重于2018年后ATR抑制剂开发中的药物化学进展.
- 化学支架和结构-活动关系的系统分析.
- 综合关于正在进行的临床试验和候选分子的信息,如berzosertib,ceralasertib和gartisertib.
主要成果:
- 自2018年以来,ATR抑制剂的药物化学取得了显著进展.
- 已经探索了各种化学支架,从而产生了强效和选择性的化合物.
- 贝尔佐塞尔蒂布 (berzosertib),拉塞尔蒂布 (ceralasertib) 和加尔蒂塞尔蒂布 (gartisertib) 是ATR抑制剂在临床试验中取得进展的关键例子.
结论:
- 持续的药物化学努力对于开发有效的ATR抑制剂至关重要.
- 了解化学支架是设计下一代抑制剂的关键,这些抑制剂具有增强的功效和选择性.
- 优化的ATR抑制剂具有改善癌症治疗结果的巨大潜力.
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