MIAMI-NATIONAL COOPERATIVE DRUG DISCOVERY GROUP--AIDS

这一药物发现计划的目的是开发和 筛选抑制生产和细胞病变作用的药物 爱滋病逆转录病毒。该提案结合了以下功能 知名调查人员的几个实验室计划 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，涉及毒品 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 在迈阿密大学合成的类似物和 英国伯明翰，分离和表征天然产物 亚利桑那大学和许多化学物质和文化 来自Upjohn存储库的过滤器，用于抗病毒和抗 病毒聚合酶活性。显示阳性的精选药物 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 对一组人类细胞系的细胞毒性。除了这4个 主要研究领域，我们建立了6个核心资源来 为参与者提供实验室和行政支持。 整个程序将快速翻译来自所有 用于新药开发的资源。尤其与新的 药物发现，建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股的I期和II期研究中 迈阿密大学验证体外筛选技术。 总而言之，提出的实验室计划代表了一种雄心勃勃的 然而，艾滋病抗病毒化疗的高度务实方法 在提供基础研究数据库的同时 对理解抗癌药物作用机制的重要意义 艾滋病的药物。

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.