Specific inhibition of heat-shock-protein 90 (Hsp90) by a novel peptidomimetic inhibitor shepherdin in malignant glioma cells

新型拟肽抑制剂 Shepherdin 对恶性胶质瘤细胞中热休克蛋白 90 (Hsp90) 的特异性抑制

• 批准号: 125479995
• 负责人: Professor Dr. Markus David Siegelin
• 金额: --
• 依托单位: Department of Pathology and Cell Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/125479995?language=en
• 关键词: Specific; inhibition; heat; shock; protein

Malignant gliomas are the most common type of brain tumors. The most common and malignant form of gliomas is known as glioblastoma multiforme (GBM), which accounts for approximately 60%–70% of the cases. Current standard-of-care therapy for GBM confers a median survival period of only 14.6 months. Heat-shock-protein 90 (Hsp90) is an attractive therapeutic target since it can bind a number of well-characterized client proteins, including many oncogenic signaling proteins being essential for progression and therapeutic resistance of GBM such as ErbB2, EGFR, Raf, MEK, PDGFR, Cdk-4, - 6, and -9, Akt, mutated p53 and survivin. Many of these proteins are the ones that are mutated or overexpressed in GBM. A novel specific inhibitor of Hsp90 is the peptidomimetic Shepherdin that has been shown to specifically target tumour cells whereas it has no effect on non-neoplastic cells. In this study Shepherdin will be evaluated as a potential new drug in treating GBM.

恶性神经胶质瘤是最常见的脑肿瘤类型。胶质瘤最常见和最恶性的形式是多形性胶质母细胞瘤（GBM），约占病例的60%-70%。目前GBM标准治疗的中位生存期仅为14.6个月。热休克蛋白90 （Hsp90）是一个有吸引力的治疗靶点，因为它可以结合许多特征明确的客户蛋白，包括许多对GBM进展和治疗耐药至关重要的致癌信号蛋白，如ErbB2、EGFR、Raf、MEK、PDGFR、Cdk-4、- 6和-9、Akt、突变p53和survivin。这些蛋白质中有许多在GBM中发生了突变或过度表达。一种新的特异性Hsp90抑制剂是拟肽蛋白，它已被证明能特异性靶向肿瘤细胞，而对非肿瘤细胞没有作用。本研究将对谢泼丁作为治疗GBM的潜在新药进行评价。