Anti-angiogenic & anti-tumor drug for human glioma

抗血管生成

• 批准号: 6625852
• 负责人: YOUZHI TONG
• 金额: $ 24.31万
• 依托单位: ANGION BIOMEDICA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2004-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625852
• 关键词: angiogenesis inhibitors; antineoplastics; apoptosis; brain neoplasms; cell proliferation; combinatorial chemistry; computer simulation; dosage; drug design /synthesis /production; drug resistance; gel electrophoresis; glioma; hepatocyte growth factor; high performance liquid chromatography; immunocytochemistry; laboratory mouse; laboratory rat; light microscopy; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neoplastic process; terminal nick end labeling; tissue /cell culture; vascular endothelium

Numerous novel approaches to cancer therapy are currently being examined including gene therapy, immunotherapy and combinations of traditional and novel therapies. By targeting multiple events in the proliferation and spread of cancer cells the effectiveness of treatments may be improved and resistance to therapy avoided. Since SF/HGF may promote tumor growth through multiple actions both on cancer cells as well as endothelial cells in the vasculature supplying the tumors., it provides an excellent therapeutic target. Many glioma cell lines contain c-met, the receptor for SF/HGF and are therefore promising targets for SH/HGF antagonism. In addition SF/HGF antagonists would also prevent proliferation of endothelial cells which are more easily accessible than tumor cells, may be targeted specifically without significant side effects, are not likely to develop drug resistance because of their genetic stability and can be targeted for different tumor types. The current grant proposes to use the novel approach of inhibition of the angiogenic and growth activities of scatter factor/hepatocyte growth factor (SF/HGF) using small molecules designed by phase display and computer modeling in order to inhibit cancer growth and enhance the effectiveness of chemotherapy. In these studies we will continue development of a compound we have already identified with SF/HGF antagonistic activity and pursue a directed screening process to identify additional SF/HGF antagonists with the goal of improved efficacy and minimal toxicity. PROPOSED COMMERCIAL APPLICATIONS: The Phase I and Phase II projects are designed to provide the key pre- clinical data to support regulatory filing and launch of clinical trials of SF/HGF and mimetic molecules for therapeutic angiogenesis. The company expects to pursue clinical development and commercialization with a pharmaceutical industry partner.

目前正在研究许多新的癌症治疗方法，包括基因疗法、免疫疗法以及传统疗法和新型疗法的组合。通过靶向癌细胞增殖和扩散中的多个事件，可以提高治疗的有效性并避免对治疗的抵抗。由于 SF/HGF 可以通过对癌细胞以及供应肿瘤的脉管系统中的内皮细胞的多种作用来促进肿瘤生长，因此它提供了一个极好的治疗靶点。许多神经胶质瘤细胞系含有 c-met（SF/HGF 受体），因此是 SH/HGF 拮抗作用的有希望的靶标。此外，SF/HGF拮抗剂还可以防止内皮细胞的增殖，内皮细胞比肿瘤细胞更容易接近，可以特异性靶向而没有明显的副作用，由于其遗传稳定性而不太可能产生耐药性，并且可以针对不同的肿瘤类型。目前的资助计划使用通过相显示和计算机建模设计的小分子抑制分散因子/肝细胞生长因子（SF/HGF）的血管生成和生长活性的新方法，以抑制癌症生长并增强治疗的有效性。化疗。在这些研究中，我们将继续开发一种我们已经鉴定出具有 SF/HGF 拮抗活性的化合物，并进行定向筛选过程来鉴定其他 SF/HGF 拮抗剂，目标是提高疗效和最小化毒性。拟议的商业应用：I 期和 II 期项目旨在提供关键的临床前数据，以支持用于治疗性血管生成的 SF/HGF 和模拟分子的监管备案和临床试验的启动。该公司希望与制药行业合作伙伴一起进行临床开发和商业化。