Whole Animal Microplate Assay for Angiogenesis

描述(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无价之宝。斑马鱼具有与包括人类在内的其他脊椎动物相似的组织和器官发育的形态和分子基础。第二阶段研究将自动化在第一阶段研究中开发的酶分析，以高通量筛选小分子化合物文库。基于微孔板的斑马鱼检测具有几个引人注目的优点，包括检测时间、药物输送和药物剂量。由于斑马鱼的繁殖和饲养成本低廉，因此可以对大量动物进行检测。第二阶段的研究还将开发补充分析，以评估“Hit”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一些验证性测试来评估药物特异性，第二阶段研究将开发一系列补充测试来充分表征潜在的抗血管生成药物。对完整的生命系统进行分析，然后再进行复杂的生命系统，如老鼠，将简化药物开发过程，并显著降低成本。 建议的商业应用： 通过提供一系列简单、快速和低成本的检测方法来识别和表征血管生成抑制物，斑马鱼检测将促进各种疾病的药物开发过程，包括癌症、心脏、眼睛、风湿和皮肤疾病。

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.