强效,选择性和口服生物可用基纳林基STK17A/B双抑制剂
Sana Chaudhry1, Jesus R Castro1, Tulasigeri M Totiger1
1Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida33136, United States.
ACS medicinal chemistry letters
|June 19, 2024
概括
研究人员开发了强大的STK17A/B抑制剂用于癌症治疗. 化合物9显示强烈的抑制和良好的口服生物可用性,使得进一步的体内癌症研究.
科学领域:
- 生物化学 生物化学
- 药用化学 医学化学
- 在瘤学瘤学.
背景情况:
- STK17A是一种新型的氨酸/氨酸激酶,在各种癌症中过度表达.
- 向STK17A为癌症治疗提供了一个潜在的治疗策略.
研究的目的:
- 发现和优化STK17A和STK17B的新型抑制剂.
- 为了识别具有癌症治疗口服生物可用性的类似药物的化合物.
主要方法:
- 基于quinazoline核心的识别. 根据quinazoline核心的识别.
- 结构-活动关系研究用于化合物优化.
- 对STK17A/B和酶面板进行酶抑制分析.
主要成果:
- 发现了强效和选择性的STK17A/B抑制剂.
- 化合物9显示STK17A IC50的23 nM. 这种结合表明STK17A IC50的23 nM.
- 化合物9表现出强烈的STK17A/B抑制,具有最小的目标外活性和良好的口服生物可用性.
结论:
- 化合物9是各种癌症体内研究的有希望的候选者.
- 开发的抑制剂为癌症治疗提供了潜在的新途径.
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