• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Novel C-4 Heteroaryl 13-cis-Retinamide Mnk/AR Degrading Agents Inhibit Cell Proliferation and Migration and Induce Apoptosis in Human Breast and Prostate Cancer Cells and Suppress Growth of MDA-MB-231 Human Breast and CWR22Rv1 Human Prostate Tumor Xenografts in Mice
【24h】

Novel C-4 Heteroaryl 13-cis-Retinamide Mnk/AR Degrading Agents Inhibit Cell Proliferation and Migration and Induce Apoptosis in Human Breast and Prostate Cancer Cells and Suppress Growth of MDA-MB-231 Human Breast and CWR22Rv1 Human Prostate Tumor Xenografts in Mice

机译：新型C-4杂芳基13-顺式视黄酰胺Mnk / AR降解剂抑制人乳腺癌和前列腺癌细胞的增殖和迁移并诱导其凋亡，并抑制MDA-MB-231人乳腺癌和CWR22Rv1人前列腺肿瘤异种移植物的生长。

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

The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most potent compounds against a variety of human breast and prostate cancer (BC/PC) cell lines were compounds 16 (VNHM-1-66), 20 (VNHM-1-81), and 22 (VNHM-1-73). In these cell lines, the compounds induce Mnk1/2 degradation to substantially suppress eIF4E phosphorylation. In PC cells, the compounds induce degradation of both full-length androgen receptor (fAR) and splice variant AR (AR-V7) to inhibit AR transcriptional activity. More importantly, VNHM-1-81 has strong in vivo antibreast and antiprostate cancer activities, while VNHM-1-73 exhibited strong in vivo antibreast cancer activity, with no apparent host toxicity. Clearly, these lead compounds are strong candidates for development for the treatments of human breast and prostate cancers.
机译：讨论了新型的C-4杂芳基13-顺式-视黄酰胺调节Mnk-eIF4E和AR信号传导的合成以及体外和体内的抗乳腺癌和抗前列腺癌活性。 C-4杂芳基取代基的修饰表明1H-咪唑对高抗癌活性至关重要。针对多种人类乳腺癌和前列腺癌（BC / PC）细胞系的最有效化合物是化合物16（VNHM-1-66），20（VNHM-1-81）和22（VNHM-1-73）。在这些细胞系中，化合物诱导Mnk1 / 2降解，从而基本上抑制eIF4E磷酸化。在PC细胞中，这些化合物可诱导全长雄激素受体（fAR）和剪接变体AR（AR-V7）降解，从而抑制AR转录活性。更重要的是，VNHM-1-81具有很强的体内抗乳腺癌和抗前列腺癌活性，而VNHM-1-73则具有很强的体内抗乳腺癌活性，没有明显的宿主毒性。显然，这些先导化合物是开发用于治疗人类乳腺癌和前列腺癌的强有力的候选药物。

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