Whole Animal Microplate Assay for Angiogenesis

描述（由申请人提供）：斑马鱼和线虫等小型模型动物已成为研究早期发展和药物发现的宝贵资源。斑马鱼的组织和器官发育的形态学和分子基础与包括人类在内的其他脊椎动物相似。二期研究将自动化在一期研究中开发的酶分析，用于小分子化合物文库的高通量筛选。基于微孔板的斑马鱼试验具有几个令人信服的优势，包括分析时间，药物传递和药物剂量。由于斑马鱼的繁殖和饲养成本不高，因此可以对斑马鱼的数量进行统计分析。二期研究还将开发补充性分析，以评估“击中”药物对肝脏毒性和整个动物发育的影响。由于全面的药物筛选计划依赖于许多验证性分析来评估药物特异性，因此二期研究将开发一系列补充分析来充分表征潜在的抗血管生成药物。在进行复杂的生命系统（如小鼠）之前，先对完整的生命系统进行分析，这将简化药物开发过程，并大大降低成本。

DESCRIPTION (provided by applicant): Small model animals such as zebrafish and nematode have become invaluable for studying early development and for drug discovery. The zebrafish has a morphological and molecular basis of tissue and organ development that is similar to other vertebrates, including humans. Phase II research will automate the enzymatic assay developed in Phase I research for high throughput screening of small molecule compound libraries. The microplate-based zebrafish assay offers several compelling advantages, including assay time, drug delivery and drug dosage. Because zebrafish are inexpensive to breed and maintain, a statistically significant number of animals can be assayed. Phase II research will also develop complementary assays to assess effects of "hit" drugs on liver toxicity and whole animal development. Since comprehensive drug screening programs rely on a number of confirmatory assays to assess drug specificity, Phase II research will develop a family of complementary assays to fully characterize potential anti-angiogenic drugs. Analysis of complete living systems, before proceeding to complex living systems, such as the mouse, will streamline the drug development process and dramatically reduce costs. PROPOSED COMMERCIAL APPLICATIONS: By providing a family of simple, rapid and inexpective assays for identifying and characterizing angiogenesis inhibitors, the zebrafish assays will facilitate the drug development process for a variety of diseases, including cancer, and heart, eye, rheumatic and skin diseases.