CORE--INHIBITOR ACQUISITION, EVALUATION AND FORMULATION

核心——抑制剂的获取、评估和配制

• 批准号: 6955355
• 负责人: JOHN P MOORE
• 金额: $ 21.78万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6955355
• 关键词: Macaca mulatta; antiAIDS agent; biomedical facility; chemoprevention; dosage forms; drug quality /standard; drug screening /evaluation; human tissue

The objectives of the Inhibitor Acquisition, Evaluation and Formulation Core are: 1) To acquire and initially characterize combinations of inhibitors of HIV-1 attachment, fusion and entry (AFE inhibitors) prior to their further evaluation as microbicide candidates in the in vitro and macaque model experimental systems; 2) To facilitate the formulation of these AFE inhibitor combinations in a way that is suitable for their testing for efficacy and safety in the macaque vaginal transmission model, then for safety in healthy women. The Core Leader will be John P. Moore, Ph.D., with Robin Shattock, Ph.D. acting as co-Leader. This Research Support Core will be located at the Weill Medical College of Cornell University, New York, NY. Its principal function will be to act as a central resource to support the individual Research Projects. The Core will obtain, by collaboration or purchase, sufficient quantities of suitable AFE inhibitors for use in all four Research Projects, including GMP-grade material when appropriate. This will ensure that a common set of reagents is used throughout the IPCP-HTM group. The Core will determine the potency of these inhibitors against a range of HIV-1 isolates in vitro, using well-established assays based on primary human and rhesus macaque lymphocytes, macrophages and dendritic cells. This work will ensure that only bona fide, active reagents are used in each of the Research Projects. The Core will identify which combinations of inhibitors are most suitable for further evaluation in the in vitro model systems (Research Projects I and II) and, in particular, in the rhesus macaque model (Research Project III). The Core will arrange expertise in microbicide formulation, and will supply properly formulated inhibitors to Research Project III, to ensure appropriate testing of candidate microbicides in the macaque vaginal transmission model. GMP grade inhibitors and formulations will be supplied to Research Project IV for clinical testing, when appropriate. The Core will also assist with the design and interpretation of experiments involving inhibitor combinations, in vitro and in the macaque.

抑制剂获取，评估和配方核心的目标是：1）在进一步评估Interro和Macaque模型实验系统中，在进一步评估HIV-1附着，融合和进入（AFE抑制剂）之前，并最初表征了HIV-1附着，融合和进入（AFE抑制剂）抑制剂的组合； 2）以适合在猕猴阴道传播模型中测试功效和安全性测试的方式，以促进这些AFE抑制剂组合的制定，然后在健康女性中安全。核心负责人将是约翰·P·摩尔博士，博士罗宾·肖托克（Robin Shattock）博士。充当共同领导者。该研究支持核心将位于纽约纽约康奈尔大学的威尔医学院。它的校长 功能将是支持各个研究项目的中心资源。核心将通过协作或购买获得足够数量的合适的AFE抑制剂，可在所有四个研究项目中使用，包括适当的GMP级材料。这将确保在整个IPCP-HTM组中使用一组常见的试剂。核心将使用基于原发性人类和猕猴淋巴细胞，巨噬细胞和树突状细胞的良好测定法确定这些抑制剂对一系列HIV-1分离株的效力。这项工作将确保只有真正的活跃试剂是 用于每个研究项目。核心将确定哪种抑制剂组合最适合在体外模型系统（研究项目I和II）中，尤其是在恒河猴猕猴模型（研究项目III）中进行进一步评估。核心将在菌心配方中安排专业知识，并将提供适当的配制抑制剂以研究项目III，以确保在猕猴阴道传播模型中适当测试候选菌心。 GMP等级抑制剂和配方将在适当的情况下提供给IV研究项目IV。核心还将有助于在体外和猕猴中设计和解释涉及抑制剂组合的实验。