基础研究 情报发生 2026-10-31 · 发布于 2026-11-01

大规模化合物筛选揭示胶质瘤敏感药物:SM1-71 等抑制剂的线索

来源:J Transl Med · PMID 42958268 · DOI 10.1186/s12967-026-08771-1 · 来源:IMA 知识库《文献层·文献监控卡片》2026-10-31 期 · 全文级(file_id dmlmcfQeUyzO,实际下载核验) · 全文已获取并通过归属校验

时间标签:数据日期 2026-10-31 · 生成时间 2026-11-01 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/10/28–2026/10/31 | 情报发生日期 2026-10-31

研究问题

Despite advances in multimodal therapy, GBM remains associated with a dismal prognosis, with a median survival of less than 2 years and a 5-year survival rate below 10% [–].;However, the survival benefit provided by this regimen remains limited.;Although temozolomide (TMZ) remains the cornerstone chemotherapeutic agent in the standard treatment of glioblastoma, acquired or intrinsic resistance to TMZ has become a major barrier to therapeutic efficacy and is closely associated with treatment failure and poor clinical outcomes [, –].

方法

Cell viability was assessed using the Cell Counting Kit-8 (CCK-8, TargetMol, C0005) assay according to the manufacturer’s instructions.;Using these two criteria, 66 compounds were selected for further ranking and annotation.;CCK-8 assays were used for three related but distinct purposes: primary single-dose screening, IC₅₀ determination, and proliferation/viability validation at selected doses.;At each endpoint, 10 µL of CCK-8 reagent was added to each well, followed by incubation for 1–4 h in the dark.

核心结论

The compounds used were sourced from the MCE company’s anti-brain tumor compound library, which includes 1,460 small molecules with clear or potential anti-brain tumor activity.;The MCE anti-brain tumor compound library was selected because it is curated to include compounds with documented or putative relevance to brain tumors, CNS tumor biology, or cancer-associated pathways.;In summary, through large-scale screening of 1,460 anti-brain tumor compounds on three cell lines, we identified the top 24 compounds with the strongest cell inhibition rates (Table ). ‖ 结论:Because normal brain-related cell controls, BBB permeability, pharmacokinetics, long-term toxicity, orthotopic glioma models, 3D neurosphere/organoid validation, and combination treatment with TMZ were not fully evaluated, these findings should be regarded as preliminary preclinical evidence supporting further investigation rather than direct evidence for clinical application.

局限

Nevertheless, inclusion in this library does not establish BBB permeability.;Accordingly, the current study should be interpreted as identifying compounds with direct anti-glioma activity under in vitro and subcutaneous in vivo conditions, while BBB penetration, brain exposure, and pharmacokinetic suitability remain essential next steps.;Importantly, during the initial screening stage, all vehicle controls were matched to the same final DMSO concentration used in the drug-treated wells, thereby minimizing solvent-related confounding.

对本项目的价值

★☆☆☆☆ 相关范围内,作为背景与横向对照收录。最大样本量约 1,460。

全文来源

PMC JATS 全文(正文 44,731 字符,已过标题/DOI 逐字归属校验)

原文题录

  • 英文标题:Large-scale compound screening reveals sensitivities to SM1-71, HDACs/mTOR Inhibitor 1, BGT226, and ON013100 in glioma.
  • 期刊与标识:J Transl Med · PMID 42958268 · DOI 10.1186/s12967-026-08771-1

B 级证据分级:B 级(同行评议临床前研究,主要为动物模型)

本文核心结论来自动物模型或体外细胞学,属临床前证据,不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义,与人类临床结局之间仍有距离。

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