4.7 Article

Virtual screening and structure-activity relationship study of novel BTK inhibitors in Traditional Chinese Medicine for the treatment of rheumatoid arthritis

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2023.2188418

关键词

Rheumatoid arthritis; Bruton's tyrosine kinase inhibitors; three-dimensional quantitative structure-activity relationship (3D-QSAR); virtual screening; molecular dynamics simulations

向作者/读者索取更多资源

This study explored the structure-activity relationships of 1-amino-1H-imidazole-5-carboxamide derivatives as BTK inhibitors and investigated Traditional Chinese Medicine prescriptions for rheumatoid arthritis. A database of 4027 ingredients was established for virtual screening, and five compounds were selected for higher precision docking. The results revealed potential BTK inhibitors that interacted with key residues and provided crucial information for developing novel BTK inhibitors.
Bruton tyrosine kinase (BTK) is a known drug target for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). In this study, a series of 1-amino-1H-imidazole-5-carboxamide derivatives with good inhibitory activity against BTK were selected to explore the structure-activity relationships of these BTK inhibitors (BTKIs). Furthermore, we concentrated on 182 prescriptions of Traditional Chinese Medicine with therapeutic effects on RA. 54 herbs with a frequency of >= 10 were counted to establish a database containing 4027 ingredients for virtual screening. Five compounds with relatively higher docking scores and better absorption, distribution, metabolism, elimination and toxicity (ADMET) parameters were then selected for higher precision docking. The results demonstrated that the potentially active molecules form hydrogen bond interactions with the hinge region residues Met477, Glu475, glycine-rich P-loop residue Val416, Lys430 and DFG motif Asp539. In particular, they also interact with the key residues Thr474 and Cys481 of BTK. The molecular dynamics (MD) results demonstrated that all five compounds above could bind with BTK stably as its cognate ligand in dynamic conditions. This work identified several potential BTKIs using a computer-aided drug design approach and may provide crucial information for developing novel BTKIs.Communicated by Ramaswamy H. Sarma

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据