Scholarlink

Background <p>Gliomas, particularly glioblastomas (GBM), are the most aggressive primary brain tumors with poor prognosis and limited therapeutic options. Resistance to temozolomide and high tumor invasiveness underscore the urgent need for novel therapeutic agents.</p> Methods <p>We performed a large-scale screening of 1,460 small-molecule compounds using three human glioma cell lines (U251, LN229, and A172) to identify candidate anti-glioma agents. Four compounds with limited prior investigation in gliomas—SM1-71 (TAK1 inhibitor), HDACs/mTOR Inhibitor 1, BGT226 (PI3K/mTOR inhibitor), and ON013100 (mitotic inhibitor)—were selected for detailed in vitro and in vivo evaluation. In vitro assays included cell viability (CCK-8), cell cycle analysis, apoptosis, migration, and invasion assays. In vivo efficacy was assessed in a subcutaneous xenograft mouse model.</p> Results <p>SM1-71, HDACs/mTOR Inhibitor 1, BGT226, and ON013100 significantly inhibited glioma cell proliferation, induced G2-phase cell cycle arrest, and promoted apoptosis. All four compounds suppressed glioma cell migration and invasion in vitro. In the xenograft model, SM1-71 and ON013100 showed the most pronounced tumor growth inhibition (~ 75% reduction), whereas BGT226 and HDACs/mTOR Inhibitor 1 exhibited moderate effects. Ki-67 immunostaining confirmed decreased tumor cell proliferation. No significant body weight loss was observed, although isolated mortality indicated the need for further toxicity evaluation.</p> Conclusions <p>This study identifies four promising anti-glioma compounds with potent in vitro and in vivo activity, particularly SM1-71 and ON013100. These findings support further preclinical investigation of these compounds, particularly with respect to pharmacokinetics, blood-brain barrier penetration, toxicity, and combination with standard therapies.</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

Large-scale compound screening reveals sensitivities to SM1-71, HDACs/mTOR Inhibitor 1, BGT226, and ON013100 in glioma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月5日

查看全文
  • Yahui Zhang,
  • Mingchen Xie,
  • Hao Han,
  • Xun Xie,
  • Jianhua Cheng,
  • Jian Xu

摘要

Background

Gliomas, particularly glioblastomas (GBM), are the most aggressive primary brain tumors with poor prognosis and limited therapeutic options. Resistance to temozolomide and high tumor invasiveness underscore the urgent need for novel therapeutic agents.

Methods

We performed a large-scale screening of 1,460 small-molecule compounds using three human glioma cell lines (U251, LN229, and A172) to identify candidate anti-glioma agents. Four compounds with limited prior investigation in gliomas—SM1-71 (TAK1 inhibitor), HDACs/mTOR Inhibitor 1, BGT226 (PI3K/mTOR inhibitor), and ON013100 (mitotic inhibitor)—were selected for detailed in vitro and in vivo evaluation. In vitro assays included cell viability (CCK-8), cell cycle analysis, apoptosis, migration, and invasion assays. In vivo efficacy was assessed in a subcutaneous xenograft mouse model.

Results

SM1-71, HDACs/mTOR Inhibitor 1, BGT226, and ON013100 significantly inhibited glioma cell proliferation, induced G2-phase cell cycle arrest, and promoted apoptosis. All four compounds suppressed glioma cell migration and invasion in vitro. In the xenograft model, SM1-71 and ON013100 showed the most pronounced tumor growth inhibition (~ 75% reduction), whereas BGT226 and HDACs/mTOR Inhibitor 1 exhibited moderate effects. Ki-67 immunostaining confirmed decreased tumor cell proliferation. No significant body weight loss was observed, although isolated mortality indicated the need for further toxicity evaluation.

Conclusions

This study identifies four promising anti-glioma compounds with potent in vitro and in vivo activity, particularly SM1-71 and ON013100. These findings support further preclinical investigation of these compounds, particularly with respect to pharmacokinetics, blood-brain barrier penetration, toxicity, and combination with standard therapies.