Zeeh Pharmaceutical Experimental Station

Zeeh药物实验站位于药学院内，旨在支持 基于大学和区域产业药物发现的早期药物开发需求 实验室。该站为华盛顿大学NCDDG带来了丰富的工业药物开发经验 工作团队，使其能够在其不断发展的战术计划中建立战略优势，以满足他们的长期需求 学期计划目标。 在NCDDG分子合成的早期阶段，一小部分班级代表 将精选天然产物化合物作为半定量开发的基础 对化合物的制备和体外评估有用的分析方法。为 通过初步体外生物活性标准的化合物，选定的具有代表性的候选者将是 测试与其体内性能有关的物理化学性质，例如溶解度和细胞 渗透率，为下游的测试工作提供一定的指导。为了进一步支持体内研究， 空间站将制备和测试约16种药物的配方(包括相关的体外稳定性)。 根据体外研究(如上所述)选出的小鼠PK/代谢研究的候选对象(PER 模型)，设定剂量约为0.5毫克/公斤。按照这样确定的、尖锐的半衰期 毒理学评估(MTD)将在小鼠身上进行(每个模型)。从这些PK/代谢和急性 毒理学结果，预计将根据化合物的半衰期和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团队实验室计划3提供协调的管理 与药学院AAALAC认可的动物设施的接口，小鼠将在其中被安置一次 动物模型已经完全发展，将支持全部或大部分育种 药代动力学(PK)的群体和实验动物群体--化合物半衰期，剂量滴定； MTD的测定；急性毒理学(MTD，非GLP)；以及小鼠药效筛选。空间站将会 还与UWCCC的生物分析(GLP)实验室协调进行血液样本分析 制定了代表PK的相关研究，并将管理数据进行分析。

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.