Large-scale compound screening reveals sensitivities to SM1-71, HDACs/mTOR Inhibitor 1, BGT226, and ON013100 in glioma.
- 1Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, China.
- 2Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, China. [email protected].
- 3Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, China. [email protected].
Abstract
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.
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BibTeX
@article{zhang2026largescale,
title = {{Large-scale compound screening reveals sensitivities to SM1-71, HDACs/mTOR Inhibitor 1, BGT226, and ON013100 in glioma.}},
author = {Yahui Zhang and Mingchen Xie and Hao Han and Xun Xie and Jianhua Cheng and Jian Xu},
journal = {Journal of translational medicine},
year = {2026},
month = aug,
doi = {10.1186/s12967-026-08771-1},
url = {https://europepmc.org/article/MED/42958268},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Large-scale compound screening reveals sensitivities to SM1-71, HDACs/mTOR Inhibitor 1, BGT226, and ON013100 in glioma.
AU - Yahui Zhang
AU - Mingchen Xie
AU - Hao Han
AU - Xun Xie
AU - Jianhua Cheng
AU - Jian Xu
PY - 2026
DA - 2026/08/05
JO - Journal of translational medicine
DO - 10.1186/s12967-026-08771-1
UR - https://europepmc.org/article/MED/42958268
AB - 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.
SN - 1479-5876
ER -