Zeeh Pharmaceutical Experimental Station

泽医药实验站

• 批准号: 7691791
• 负责人: Hana Van Campen
• 金额: $ 14.81万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7691791
• 关键词: Acute; Animal Model; Animal Testing; Animals; Biological; Biological Assay; Biological Factors; Biological Markers; Blood specimen; Breeding; Cells; Chemoprevention; Class; Clinical Trials; Data Analyses; Development; Doctor of Pharmacy; Dose; Drug Formulations; Drug Kinetics; Drug effect disorder; Evaluation; Goals; Half-Life; Health Sciences; In Vitro; Industry; Laboratories; Metabolism; Methodology; Modeling; Mus; New Agents; Numbers; Performance; Permeability; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenetics; Pharmacologic Substance; Pharmacy Schools; Population; Preparation; Property; Research Personnel; Sampling; Screening procedure; Services; Solubility; Staging; Testing; Titrations; Toxic effect; Toxicology; Universities; Work; animal facility; base; design; drug development; drug discovery; experience; in vivo; instrument; instrumentation; once housed; programs; research study

The Zeeh Pharmaceutical Experiment Station, located within the School of Pharmacy, is designed to support the early-stage pharmaceutical development needs of University-based and regional industry drug discovery laboratories. The Station brings substantial industrial drug development experience to the UW NCDDG working team, enabling it to build strategic advantage into their evolving tactical plans in meeting their long term program goals. In the early stages of the NCDDG molecule synthesis effort, a small number of class-representative natural product compounds will be carefully selected and used as the basis for the development of semiquantitative analytical methodology useful for preparation and in vitro assessment of the compounds. For compounds passing the initial in vitro biological activity criteria, selected representative candidates will be tested for their physicochemical properties which relate to their performance in vivo, e.g. solubility and cell permeability, to offer some guidance to the downstream testing work. In further support of in vivo studies, the Station will prepare and test (including relevant stability in vitro) formulations of approximately 16 drug candidates selected on the basis of in vitro studies (as above) for studies of PK/metabolism in mice (per model) at a set dose of approximately 0.5 mg/kg. In accordance with the half-lives so determined, acute toxicology evaluation (MTD) will follow in mice (per model). From these PK/metabolism and acute toxicology results, it is expected that 12 compounds will be chosen based on their half-life and MTD for study in the four animal efficacy models. Station will also provide the UW NCDDG team Lab Program 3 with a coordinated administrative interface to the School of Pharmacy AAALAC-accredited animal facility in which mice will be housed once the animal models have been fully developed and will support all or a large proportion of the breeding colonies and test animal populations for pharmacokinetics (PK) - compound half-life, dose titration; determination of MTD; acute toxicology (MTD, non-GLP); and mouse efficacy screening. The Station will also coordinate with the Bioanalytical (GLP) laboratory in the UWCCC for the analysis of blood samples drawn on behalf of the PK-related studies, and will manage the data analysis.

Zeeh制药实验站位于药学院内，旨在支持 基于大学和区域工业药物发现的早期药物开发需求 laboratories.该站为UW NCDDG带来了丰富的工业药物开发经验 工作团队，使其能够在不断发展的战术计划中建立战略优势， 长期计划目标。 在NCDDG分子合成工作的早期阶段，少数具有代表性的 天然产物化合物将被仔细选择，并用作半定量开发的基础。 用于制备和体外评价化合物的分析方法。为 通过初始体外生物活性标准的化合物，将选择代表性候选物， 测试与其体内性能相关的理化性质，例如溶解度和细胞毒性。 渗透率，以提供一些指导下游测试工作。为了进一步支持体内研究， 该站将制备和测试（包括有关体外稳定性）约16种药物的配方 根据体外研究（如上所述）选择的候选人用于小鼠PK/代谢研究（根据 模型），设定剂量约为0.5 mg/kg。根据如此确定的半衰期， 随后在小鼠中进行毒理学评价（MTD）（每个模型）。从这些PK/代谢和急性 根据毒理学结果，预计将根据其半衰期和MTD选择12种化合物进行研究 在四种动物功效模型中。 空间站还将为UW NCDDG团队实验室项目3提供协调的管理 接口的药学院AAALAC认可的动物设施，其中小鼠将被安置一次 动物模型已经得到充分开发，将支持所有或大部分育种工作， 菌落和测试动物群体的药代动力学（PK）-化合物半衰期、剂量滴定; MTD测定;急性毒理学（MTD，非GLP）;和小鼠功效筛选。该站将 还与UWCCC的生物分析（GLP）实验室协调，以分析血液样本 代表PK相关研究绘制，并将管理数据分析。