Practical formulations of HIV-1 entry inhibitors

HIV-1进入抑制剂的实用制剂

• 批准号: 7667094
• 负责人: Mark Mitchnick
• 金额: $ 31.07万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-23 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7667094
• 关键词: Animal Model; Biological Markers; Biological Models; Biology; CXCR4 gene; Cells; Cervical; Chemistry; Clinical Trials; Collaborations; Condition; Cultured Cells; Daily; Dendritic Cells; Development; Devices; Doctor of Philosophy; Drug Formulations; Elements; Epithelial; Epithelium; Evaluation; Event; Funding; Future; Genomics; Goals; HIV-1; Head; Histocompatibility; Human; Immunology; In Situ; In Vitro; Individual; Infection; Infection prevention; International; Investigation; Knowledge; Langerhans cell; Learning; Length; Localized; Location; Macaca; Macaca mulatta; Measurement; Mediating; Melissa; Methods; Modeling; Monitor; Mononuclear; Mucous Membrane; Mucous body substance; Numbers; Outcome; Pathway interactions; Pattern; Penetration; Peptides; Performance; Phase; Phase III Clinical Trials; Physiological; Population; Principal Investigator; Process; Property; Purpose; Range; Research; Research Project Grants; Robin bird; Role; Safety; Savings; Science; Scientist; Seminal fluid; Series; Sexual Transmission; Solid; Solvents; Support of Research; System; T-Lymphocyte; Technology; Testing; Thinking; Time; Tissue Model; Tissues; U-Series Cooperative Agreements; United States National Institutes of Health; Vagina; Vaginal Ring; Validation; Viral; Virus; Virus Diseases; Week; Work; base; cell type; cellulose sulfate; chemokine; comparative; controlled release; cost; cytokine; design; efficacy trial; immune function; in vitro Model; in vivo; inhibitor/antagonist; macrophage; member; microbial; microbicide; particle; pathogen; pre-clinical; prevent; programs; receptor; rectal; research clinical testing; research study; response; small molecule; transmission process; uptake; virology

This IPCP-HTM application made in response to RFA Al-oy-ooi contains three Research Projects, one Scientific Core and an Administrative Core, under the direction of Principal Investigator, John P. Moore, PhD and co-Principal Investigator, Robin A. Shattock, PhD. The purpose of the program is to conduct in vitro and in vivo pre-clinical and animal model-based research intended to facilitate the development of a vaginal microbicide based on the use of inhibitors of HIV-i entry, applied alone and/or in combination. Our goal is to use our collective knowledge of virology, immunology, formulation chemistry and mammalian biology to help develop a mechanism-based, HIV-i-specific microbicide(s). An emphasis will be the development and evaluation of long-lasting microbicide formulations and delivery methods, such as controlled release vaginal rings that can provide a continuous and constant supply of active compounds in situ for a period of weeks/months after the application of a single device, and semi-solid formulations that could be applied once-daily or even less frequently. The inhibitors that we will study include, but may not be limited to: the small molecule CCRs inhibitor, CMPDi67 (Merck); the small molecule attachment inhibitor BMS-C (Bristol-Myers Squibb); the small molecule CXCR4 inhibitor AMD3465 (AnorMED); the gp4i-based peptide fusion inhibitor, T-1249 (Trimeris). We propose: Research Project I: Robin Shattock, Characterization of entry inhibitors in human cervical and rectal tissue models, and in dendritic cells; Research Project II: Karl Malcolm, Practical Formulations of HIV-i Entry Inhibitors; Research Project III: Ronald Veazey, Testing practical microbicides in macaques; Virology and Immunology Core: John P. Moore; Administrative Core: John P. Moore. Other senior members of the team include Melissa Robbiani and Mark Mitchnick (Particle Sciences, Inc) who will participate in Research Projects I and III, respectively, under Cooperative Agreements, and Steven Wolinsky who will take part in the Virology and Immunology Core, also under a Cooperative Agreement. The involvement of Particle Sciences fulfills the mandated corporate element of the proposed research program. If this application is successfully peerreviewed and approved for support by the NIH, the International Partnership for Microbicides will provide the majority of the funding required to support the research programs headed by Drs. Shattock, Robbiani and Wolinsky, as outlined in the Program Overview section of the application.

该 IPCP-HTM 申请是针对 RFA Al-oy-ooi 的回应，其中包含三个研究项目，其中一个 科学核心和行政核心，在首席研究员 John P. Moore 的指导下， 博士兼联合首席研究员 Robin A. Shattock 博士。该计划的目的是在 体外和体内临床前和基于动物模型的研究，旨在促进开发 基于使用HIV-i进入抑制剂的阴道杀微生物剂，单独和/或组合应用。 我们的目标是利用我们在病毒学、免疫学、配方化学和 哺乳动物生物学，帮助开发基于机制的 HIV-i 特异性杀菌剂。强调将 开发和评估长效杀菌剂配方和递送方法，例如 控释阴道环，可以连续不断地供应活性化合物 使用单一装置后原位持续数周/数月，以及半固体制剂 可以每天使用一次，甚至可以降低频率。我们将研究的抑制剂包括但可能不包括 限于：小分子CCRs抑制剂，CMPDi67(Merck)；小分子附着 抑制剂 BMS-C (百时美施贵宝);小分子 CXCR4 抑制剂 AMD3465 (AnorMED)；这 基于 gp4i 的肽融合抑制剂，T-1249 (Trimeris)。我们建议：研究项目 I：Robin Shattock， 人类宫颈和直肠组织模型以及树突状细胞中进入抑制剂的表征； 研究项目 II：Karl Malcolm，HIV-i 进入抑制剂的实用配方；研究项目三： Ronald Veazey，在猕猴身上测试实用的杀菌剂；病毒学和免疫学核心：John P. 摩尔；行政核心：约翰·P·摩尔。该团队的其他高级成员包括 Melissa Robbiani 和 Mark Mitchnick（粒子科学公司）将参与研究项目 I 和 III， 分别根据合作协议，史蒂文·沃林斯基（Steven Wolinsky）将参加病毒学和 免疫学核心，也根据合作协议。粒子科学的参与满足了 拟议研究计划的强制共同要素。如果该申请成功通过同行评审 并获得 NIH 的支持，国际杀微生物剂合作伙伴关系将 提供支持博士领导的研究项目所需的大部分资金。沙托克, Robbiani 和 Wolinsky，如申请的“计划概述”部分所述。