一种STAT3 CCD结构域小分子抑制剂HB在制备治疗脑胶质瘤药物中的应用

By using hygromycin B, a small molecule inhibitor of the STAT3 CCD domain, to disrupt the CHI3L1-STAT3 interaction, the problem of existing drugs ignoring the immunosuppressive microenvironment was solved, thus achieving effective treatment for glioblastoma.

CN119258080BActive Publication Date: 2026-07-17THE SECOND AFFILIATED HOSPITAL TO NANCHANG UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
THE SECOND AFFILIATED HOSPITAL TO NANCHANG UNIV
Filing Date
2024-09-02
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

Existing drugs fail to effectively consider the immunosuppressive microenvironment surrounding the tumor when treating glioblastoma, leading to treatment failure. Furthermore, traditional drugs neglect the role of macrophages in PMT.

Method used

Hygromycin B (HB), a small molecule inhibitor of the STAT3 CCD domain, disrupts the CHI3L1-STAT3 interaction by forming hydrogen bonds with T145, T152, T265, and T272, thereby inhibiting the survival of GBM cells and the immunosuppressive microenvironment.

Benefits of technology

It effectively blocks the interaction between CHI3L1 and STAT3, inhibits tumor growth, reduces STAT3 phosphorylation and immunosuppressive marker expression in MES50 cells, and prolongs the survival of mice.

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Abstract

本发明属于肿瘤治疗领域，具体涉及一种STAT3CCD结构域小分子抑制剂潮霉素B(HB)在制备治疗脑胶质瘤药物中的应用。经研究表明，HB可以与T145、T152、T265和T272形成氢键，HB以剂量依赖的方式对GBM细胞的存活率表现出强烈的抑制作用，表明HB是一种可能破坏CHI3L1‑STAT3相互作用的潜在小分子；进一步地，HB显著降低了CHI3L1诱导的MES50细胞中STAT3的磷酸化、p‑STAT3的核积累以及CD44和SPP1的表达水平。当原位注射时，HB的给药以剂量依赖的方式显著减小了肿瘤大小并提高了生存率。即本发明为治疗胶质母细胞瘤提供了新的手段和思路。
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