COOPERATIVE DRUG DISCOVERY GROUP--AIDS

一个多机构小组寻求重新资助一个非常成功的 正在进行的合作，已经确定了临床候选人， 治疗HIV-1感染，即，U-87201 E，一种非核苷类的 HIV-1逆转录酶（RT）。 该提案包含4个项目， 代表一个综合的，合理的计划，以确定，评估和优化 HIV复制的新型抑制剂。 Upjohn实验室的四个项目将主要寻求 鉴定和优化的抗病毒和药物特性 HIV的必需核糖核酸酶H（RNase H）活性的抑制剂 RT. 这些项目将相互结合，并使用“结构- “驱动药物设计范式”将先导抑制剂开发成药物 候选人 研究RT亚基相互作用，因为它涉及 进行逆转录的控制。 开发新 已经在Upjohn化学品中鉴定的RT抑制剂类别 将评估清单中抑制HIV RT的新机制。 这些项目共同代表了一批研究人才， 在任何一个机构都可以做到。 这一群体的经验和 他们在艾滋病研究领域的记录生产力，确保这一点 计划将继续取得成功。

A multi-institutional group seeks to renew funding of a very successful ongoing collaboration that has already identified a clinical candidate for treating HIV-1 infection, i.e., U-87201E, a nonnucleoside inhibitor of the HIV-1 reverse transcriptase (RT). This proposal contains 4 projects that represent an integrated, rational plan to identify, evaluate, and optimize novel inhibitors of HIV replication. Four of the project at Upjohn Laboratories will principally seek to identify and optimize the antiviral and pharmaceutical properties of inhibitors of the essential ribonuclease H (RNase H) activity of the HIV RT. These projects will integrate with one another and use a "Structure- Driven Drug Design Paradigm" to develop lead inhibitors into drug candidates. Studies investigating RT subunit interaction as it relates to the control of reverse transcription will be performed. Work on new classes of RT inhibitors already identified in the Upjohn chemical inventory will be evaluated for novel mechanisms of inhibiting the HIV RT. Together these projects represent a group of research talents not attainable at any single institution. The experience of this group and their documented productivity in the AIDS research area, insure this program will continue to be successful.