Scholarlink

<p>The highly aggressive primary brain tumor, glioma, presents significant therapeutic challenges, particularly in its diffuse form, which remains resistant to curative treatment even after surgical intervention. Conventional approaches such as surgery, radiotherapy, and chemotherapy often fail to achieve satisfactory outcomes, underscoring the urgent need for more effective targeted therapies. In this study, we have developed novel AKT inhibitors—compounds 3260-0411, V012-5231, and V016-4965. These compounds demonstrate a substantial reduction in both AKT protein and mRNA levels in U251 and T98G glioma cells. Furthermore, our in vitro experiments reveal that these inhibitors effectively suppress AKT1 enzyme activity and induce apoptosis in glioma cells. Molecular dynamics simulations indicate that all three compounds exhibit excellent dynamic stability when bound to AKT; notably V016-4965 demonstrates the highest binding stability among them. Collectively, our findings suggest that compounds 3260-0411, V012-5231, and V016-4965 hold great promise as targeted therapies against AKT for treating glioma—a challenging malignancy with limited management options.</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

Structure-based drug design of small molecule AKT1 inhibitors to treat glioma

  • 期刊论文

  • 发表日期：

    2025年8月19日

查看全文
  • Xiuzhi Jia,
  • Qinglian Han,
  • Xiaoqun Ma,
  • Zhongwen Sun

摘要

The highly aggressive primary brain tumor, glioma, presents significant therapeutic challenges, particularly in its diffuse form, which remains resistant to curative treatment even after surgical intervention. Conventional approaches such as surgery, radiotherapy, and chemotherapy often fail to achieve satisfactory outcomes, underscoring the urgent need for more effective targeted therapies. In this study, we have developed novel AKT inhibitors—compounds 3260-0411, V012-5231, and V016-4965. These compounds demonstrate a substantial reduction in both AKT protein and mRNA levels in U251 and T98G glioma cells. Furthermore, our in vitro experiments reveal that these inhibitors effectively suppress AKT1 enzyme activity and induce apoptosis in glioma cells. Molecular dynamics simulations indicate that all three compounds exhibit excellent dynamic stability when bound to AKT; notably V016-4965 demonstrates the highest binding stability among them. Collectively, our findings suggest that compounds 3260-0411, V012-5231, and V016-4965 hold great promise as targeted therapies against AKT for treating glioma—a challenging malignancy with limited management options.