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.
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