...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Discovery of Novel Indazoles as Potent and Selective PI3K delta Inhibitors with High Efficacy for Treatment of Hepatocellular Carcinoma
【24h】

Discovery of Novel Indazoles as Potent and Selective PI3K delta Inhibitors with High Efficacy for Treatment of Hepatocellular Carcinoma

机译：Discovery of Novel Indazoles as Potent and Selective PI3K delta Inhibitors with High Efficacy for Treatment of Hepatocellular Carcinoma

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相关主题

摘要

PI3K delta inhibitors have been developed for treatment of B-cell malignancies and inflammatory and autoimmune diseases. However, their therapeutic role in solid tumors like hepatocellular carcinoma (HCC) is rarely reported. Thus, the development of potent and selective PI3K delta inhibitors with a new chemotype and therapy is highly desirable. Through the scaffold-hopping strategy, indazole was first described as the core structure of propeller-shaped PI3K delta inhibitors. A total of 26 indazole derivatives were designed and prepared to identify a novel compound 9x with good isoform selectivity, PK profile, and potency. Compared to Idelalisib and Sorafenib, the pharmacodynamic (PD) studies showed that 9x exhibits superior efficacy in HCC cell lines and xenograft models, and the mechanistic study showed that 9x robustly suppresses the downstream AKT pathway to induce subsequent apoptotic cell death in HCC models. Therefore, this work provides a new structural design of PI3K delta inhibitors for a novel and efficient therapeutic small molecule toward HCC.

著录项

获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号