发现和YK-2168的临床前资料,一个差异化的选择性CDK9抑制剂在临床开发中
Yingchun Liu1, Zhaobing Xu1, Lihong Hu1
1WuXi AppTec, 666 Gaoxin Road, East Lake High-tech Development Zone, Wuhan 430075, China.
Bioorganic & medicinal chemistry letters
|September 2, 2024
概括
一种新型的阿赞醇CDK9抑制剂,YK-2168,在临床前癌症模型中显示出更好的选择性和有效性. 这种药物目前正在临床开发中,为癌症治疗提供了一个有前途的新选择.
科学领域:
- 药用化学 医学化学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 选择性CDK9抑制显示出癌症治疗的前景.
- 现有的CDK9抑制剂因毒性和缺乏明确的临床获胜者而面临挑战.
- 需要具有差异化特征的新型药物.
研究的目的:
- 设计和合成一系列新的选择性CDK9抑制剂.
- 为了确定具有更好的选择性和药理动力学特性的临床前候选药物.
- 在固体瘤模型中评估新药的疗效.
主要方法:
- 新型阿赞醇化合物的设计和合成.
- 结构-活动关系 (SAR) 研究以确定主要候选人.
- 在胃癌细胞系异种移植模型中对CDK9选择性,体内药理动力学 (PK) 和疗效的临床前评估.
主要成果:
- 开发了一种新的选择性CDK9抑制剂的新型阿赞醇系列.
- 与AZD4573和BAY1251152.2相比,YK-2168显示出更高的CDK9选择性.
- 在临床前胃癌模型中,YK-2168表现出差异化的静脉注射PK配置文件和显著的固体瘤疗效.
结论:
- YK-2168代表了一个有前途的临床前候选人,其CDK9选择性和有效性得到改善.
- 这种新型的阿桑多尔支架为癌症治疗提供了潜在的新疗法途径.
- 目前,YK-2168正在中国进行临床开发.
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