• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Novel potent HIF-1 inhibitors for the prevention of tumor metastasis: discovery and optimization of 3-aryl-5-indazole-1,2,4-oxadiazole derivatives
【24h】

Novel potent HIF-1 inhibitors for the prevention of tumor metastasis: discovery and optimization of 3-aryl-5-indazole-1,2,4-oxadiazole derivatives

机译：用于预防肿瘤转移的新型有效HIF-1抑制剂：3-芳基-5-吲唑-1,2,4-恶二唑衍生物的发现和优化

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

摘要

Hypoxia inducible factor-1 (HIF-1) is the key transcription factor of cellular response to hypoxia and plays a critical role in tumor metastasis. We describe here the discovery and a structure-activity relationship study of a series of 3-aryl-5-indazole-1,2,4-oxadiazole derivatives as novel HIF-1 inhibitors. The two most promising compounds 4g and 4h inhibit HIF-1 transcription with IC50 values of 0.62 and 0.55 mu M in vitro, respectively, and they exhibit more efficient HIF-1 inhibition in xenograft tumors than YC-1, a potential anticancer drug targeting HIF-1. In addition, they also remarkably prevent the hypoxia-driven migration of SKOV3 cells in vitro and tumor metastasis in vivo. Further investigation of the mechanism revealed that the two inhibitors could decrease HIF-1 alpha and VEGF expression. These results suggest that our newly synthesized HIF-1 inhibitors 4g and 4h are potential therapeutic agents with which to treat tumor metastasis.
机译：缺氧诱导因子-1（HIF-1）是细胞对缺氧反应的关键转录因子，在肿瘤转移中起关键作用。我们在这里描述了一系列新型HIF-1抑制剂3-芳基-5-吲唑-1,2,4-恶二唑衍生物的发现和构效关系研究。两种最有希望的化合物4g和4h在体外抑制HIF-1转录，其IC50值分别为0.62和0.55μM，并且它们在异种移植肿瘤中显示出比YC-1更有效的HIF-1抑制作用，YC-1是靶向HIF的潜在抗癌药物-1。此外，它们还显着防止了体外低氧驱动的SKOV3细胞迁移和体内肿瘤转移。对该机理的进一步研究表明，这两种抑制剂可以降低HIF-1α和VEGF的表达。这些结果表明，我们新合成的HIF-1抑制剂4g和4h是治疗肿瘤转移的潜在治疗剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
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