SCREENING AND DRUG DESIGN OF HIV-1 THERAPEUTICS

HIV-1 疗法的筛选和药物设计

• 批准号: 3546714
• 负责人: WILLIAM A. HASELTINE
• 金额: $ 76.06万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3546714
• 关键词: AIDS; antiAIDS agent; antiviral agents; cooperative study; drug design /synthesis /production; drug screening /evaluation; human immunodeficiency virus 1

A multi-institutional group seeks to renew funding to support the continuation of its cooperative effort to develop novel classes of drugs which inhibit HIV-1 replication. This proposal consists of 5 projects that represent an integrated program using a rational approach to develop anti-HIV-1 drugs. Three of the projects based at academic institutions will apply fundamental knowledge to the development of biochemical and cell based assays for key components of HIV-1. Specific targets include the HIV-1 integrase, vpr protein, capsid packaging functions and ribonucleaseH. Work on reverse transcriptase and gp120-CD4 interactions will continue as well as work on selected new areas in the design of protease inhibitors. The fourth project based at an academic institution will address problems of resistance of HIV-1 to anti-viral therapy. To this end, fundamental studies of drug resistance will be carried out. Strains of SIV resistant to anti-viral drugs will be made, and an animal model, SIVMac, will be used to develop means of overcoming clinical resistance. The industrial partner is well equipped to apply the latest methods of drug development to HIV-1 therapy and is experienced in bringing drugs from the development state to clinical trials. The group includes three laboratories from the Dana-Farber Cancer Institute, one laboratory from Columbia University, and scientists at SmithKline Beecham Pharmaceuticals. The group also includes sub-projects to be carried out at the Delta Regional Primate Research Center and at the Albert Einstein College of Medicine. Together these institutions provide a pool of research unattainable at any single institution. The experience and proven ability of this group to work together productively insures that this program will continue to be successful.

一个多机构的团体试图续签资金来支持 继续开发新型药物的合作努力 抑制HIV-1复制。 该建议由5个代表集成计划的项目组成 使用有理方法开发抗HIV-1药物。 三个 基于学术机构的项目将把基本知识应用于 开发基于生化和细胞的基于细胞的测定 HIV-1。 特定靶标包括HIV-1积分酶，VPR蛋白，capsid 包装功能和核糖核酸酶。 在逆转录酶和 GP120-CD4互动将继续以及在选定的新领域进行工作 在蛋白酶抑制剂的设计中。 基于学术机构的第四个项目将解决问题 HIV-1对抗病毒疗法的抗性。 为此，基本 将进行耐药性研究。 抗SIV菌株 将生产抗病毒药物，并将使用动物模型SIVMAC 开发克服临床抵抗的手段。 工业合作伙伴有能力应用最新的药物方法 开发HIV-1疗法，并经验丰富 发展状态到临床试验。 该小组包括来自Dana-Farber癌的三个实验室 研究所，一名来自哥伦比亚大学的实验室，科学家 Smithkline Beecham Pharmaceuticals。 该组还包括子项目 将在三角洲地区灵长类动物研究中心和 阿尔伯特·爱因斯坦医学院。 这些机构一起提供 任何单个机构都无法实现的研究库。 经验 并证明了该小组共同努力的能力，可以确保 该计划将继续取得成功。