...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Future medicinal chemistry >Design and synthesis of a new series of highly potent RAF kinase-inhibiting triarylpyrazole derivatives possessing antiproliferative activity against melanoma cells
【24h】

Design and synthesis of a new series of highly potent RAF kinase-inhibiting triarylpyrazole derivatives possessing antiproliferative activity against melanoma cells

机译：设计和合成具有抑制黑色素瘤细胞增殖活性的新型高效抑制RAF激酶的三芳基吡唑衍生物

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

Background: Inhibition of V600E-B-RAF kinase represents a potential avenue for melanoma treatment. Herein, a series of 1,3,4-triarylpyrazoles possessing amide linker were designed, synthesized and evaluated for RAF kinase inhibition. Results: Compounds 1d and 1f were more potent than sorafenib against A375 cell line, and their selectivity indexes toward A375 than HS27 fibroblasts were 25.43 and 45.83, respectively. Compound 1f was more potent against the melanoma cell lines with B-RAF V600E mutation than melanoma cells with NRAS mutation and normal skin epithelial cells. Compounds 1d and 1f showed strong potency and selectivity against V600E-B-RAF kinase with IC50 values of 3.80 and 2.98 nM, respectively. Molecular docking studies revealed their binding mode. Conclusion: Potent and selective V600E-B-RAF antimelanoma agents were discovered.
机译：背景：抑制V600E-B-RAF激酶代表了黑色素瘤治疗的潜在途径。本文中，设计，合成了一系列具有酰胺连接基的1,3,4-三芳基吡唑，并对其RAF激酶抑制进行了评估。结果：化合物1d和1f对索拉非尼对A375细胞的作用更强，并且对HSK27成纤维细胞的对A375的选择性指数分别为25.43和45.83。与具有NRAS突变的黑素瘤细胞和正常皮肤上皮细胞相比，化合物1f对具有B-RAF V600E突变的黑素瘤细胞系更有效。化合物1d和1f对V600E-B-RAF激酶显示出强效价和选择性，IC50值分别为3.80和2.98 nM。分子对接研究揭示了它们的结合模式。结论：发现了有效的和选择性的V600E-B-RAF炭疽病药物。

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