Scholarlink

<p>CBL-B is an E3-ubiquitin ligase that serves a key role in modulating immune response by negatively inhibiting effector T-cell activation. Inhibitors of CBL-B would be an effective way for immune activation, making it a promising target for cancer immunotherapy and other related immune diseases. In this study, we sought to identify potential inhibitors of CBL-B through structure-based virtual screening, molecular docking, ADMET analysis, molecular dynamics simulation, and MM/GBSA calculations. A diverse set of compounds was screened against CBL-B using molecular docking augmented by a machine-learning scoring function (RF-score). The top leads were further evaluated for their ADMET properties resulting in three compounds that were subjected to a 100&#xa0;ns MD simulation. MD results revealed the stability of protein–ligand complexes. Finally, MM/GBSA calculations resulted in higher free binding energy for the three compounds compared to the cocrystallized ligand, implying better affinity towards CBL-B and suggesting the use of these compounds as novel inhibitors of CBL-B.</p><p><i>Clinical trial number</i>:&#xa0;Not applicable.&#xa0;</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A computational study to identify potential inhibitors targeting the TKB domain of CBL-B

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月2日

查看全文
  • Sherif Elsabbagh

摘要

CBL-B is an E3-ubiquitin ligase that serves a key role in modulating immune response by negatively inhibiting effector T-cell activation. Inhibitors of CBL-B would be an effective way for immune activation, making it a promising target for cancer immunotherapy and other related immune diseases. In this study, we sought to identify potential inhibitors of CBL-B through structure-based virtual screening, molecular docking, ADMET analysis, molecular dynamics simulation, and MM/GBSA calculations. A diverse set of compounds was screened against CBL-B using molecular docking augmented by a machine-learning scoring function (RF-score). The top leads were further evaluated for their ADMET properties resulting in three compounds that were subjected to a 100 ns MD simulation. MD results revealed the stability of protein–ligand complexes. Finally, MM/GBSA calculations resulted in higher free binding energy for the three compounds compared to the cocrystallized ligand, implying better affinity towards CBL-B and suggesting the use of these compounds as novel inhibitors of CBL-B.

Clinical trial number: Not applicable.