Anti-angiogenic & anti-tumor drug for human glioma

目前正在研究许多新的癌症治疗方法，包括基因治疗，免疫治疗以及传统和新疗法的组合。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抗性。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，它提供了极好的治疗靶点。许多胶质瘤细胞系含有c-met，SF/HGF的受体，因此是SH/HGF拮抗作用的有希望的靶点。此外，SF/HGF拮抗剂还将防止内皮细胞的增殖，所述内皮细胞比肿瘤细胞更容易接近，可以被特异性靶向而没有显著的副作用，由于其遗传稳定性而不太可能产生耐药性，并且可以靶向不同的肿瘤类型。目前的资助建议使用新的方法抑制血管生成和生长活性的散射因子/肝细胞生长因子（SF/HGF）使用小分子设计的相位显示和计算机建模，以抑制癌症的生长和增强化疗的有效性。在这些研究中，我们将继续开发我们已经确定具有SF/HGF拮抗活性的化合物，并进行定向筛选过程以确定其他SF/HGF拮抗剂，目的是提高疗效和降低毒性。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SF/HGF和模拟分子用于治疗性血管生成的临床试验的监管备案和启动。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。

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.