MIAMI-NATIONAL COOPERATIVE DRUG DISCOVERY GROUP--AIDS

该药物发现计划的目的是开发和 筛选药物，将抑制生产和细胞病变效应 艾滋病逆转录病毒。 该提案结合了 几个实验室项目的既定研究者， 在药物合成，分析药理学， 实验性化疗和逆转录病毒学 拟议的计划包括四个主要领域， 合成，体外筛选，生物学研究和细胞 药理学 我们建议评估一系列核苷 类似物在迈阿密大学合成， 伯明翰，英国，天然产物分离和表征， 亚利桑那大学和一系列的化学品和文化 来自UpJohn储存库的抗病毒和抗- 病毒聚合酶活性。 显示阳性的选定药物 抗病毒和/或抗病毒聚合酶活性将进一步 研究了它们的运输特性、代谢和 这是针对一组人细胞系的细胞毒性。 除了这四个 主要研究领域，我们建立了6个核心资源， 为参与者提供实验室和行政支持。 整个程序将迅速翻译来自所有 用于新药开发。 特别是与新的 药物发现，拟议的小组可以评估临床结果 在美国国立卫生研究院药物评价部门的I期和II期研究中， 迈阿密大学验证体外筛选技术。 联合起来，提出的实验室计划代表了一个雄心勃勃的 艾滋病抗病毒化疗的一种高度实用的方法 同时提供基础研究数据库 对于理解抗肿瘤的作用机制至关重要， 艾滋病药物。

The purpose of this Drug Discovery Program is to develop and screen drugs which will inhibit production and cytopathic effects of the AIDS retrovirus. The proposal combines the capabilities of several laboratory programs of established investigators with proven track record in drug synthesis, analytical pharmacology, experimental chemotherapy and retrovirology. The proposed program consists of four major areas covering drug synthesis, in vitro screening, biological studies and cellular pharmacology. We propose to evaluate a series of nucleoside analogs synthesized at the University of Miami and Birmingham,U.K, natural products isolated and characterized at the University of Arizona and a host of chemicals and culture filterates from UpJohn repository for their anti-viral and anti- viral polymerase activity. Selected drugs which show positive anti-viral and/or anti-viral polymerase activity will be further studied for their transport characteristics, metabolism and cytotoxicity against a panel of human cell lines. Besides these 4 major research areas, we have established 6 core resources to provide laboratory and administrative support to the participants. The overall program will rapidly translate information from all sources into new drug development. Particularly relevant to new drug discovery, the proposed group can evaluate clinical outcome in phase I and II studies in the NIH Drug Evaluation Unit at the University of Miami to validate the in vitro screening techniques. Jointly, the laboratory programs proposed represent an ambitious yet highly pragmatic approach to antiviral chemotherapy for AIDS at the same time as providing the basic research database essential for understanding the mechanisms of action of anti- AIDS' drugs.