...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Bulletin of the National Research Centre >Docking-based strategy to design novel flavone-based arylamides as potent V600E-BRAF inhibitors with prediction of their drug-likeness and ADMET properties
【24h】

Docking-based strategy to design novel flavone-based arylamides as potent V600E-BRAF inhibitors with prediction of their drug-likeness and ADMET properties

机译：Docking-based strategy to design novel flavone-based arylamides as potent V600E-BRAF inhibitors with prediction of their drug-likeness and ADMET properties

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相关主题

摘要

Abstract Background V600E-BRAF protein target has much potential for scientific research as therapeutic target due to its involvement in human melanoma cancer. In the current research, molecular docking investigation was conducted on some flavone-based arylamides as anticancer drug candidates via V600E-BRAF inhibition with the help of docking software Molegro Virtual Docker. Based on the predicted results, existing structures were modified and screened for pharmacokinetics ADMET properties.Results The docking result demonstrates that compound 28 best inhibits V600E-BRAF when compared with other compounds within the dataset. This compound was used as a template in designing novel anticancer compounds by attaching some favorable substituents. The docking results of the designed compounds revealed a good MolDock score (< − 90), which showed that all the compounds can efficiently bind with the active sites of the target, out of which two analogous (N1 and N3) were considered optimal that outperformed vemurafenib, the FDA-approved V600E-BRAF inhibitor. Furthermore, these compounds passed the drug-likeness criteria (Lipinski’s rule) successfully and were found to be orally bioavailable. Also, the designed compounds were found to have good pharmacokinetics absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.Conclusion Thus, this study identified compounds (N1 and N3) as the best hits against V600E-BRAF kinase with enhanced pharmacological properties and recommends their synthesis, in vivo and ex vivo evaluation to validate our hypothesis.

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