The Pharmacology Core facility will be responsible for the design, execution, and analysis of experiments that address metabolic stability, general in i//Vo toxicity, pharmacokinetics, and in vivo efficacy of anti-cancer compounds generated by this Program Project Grant (PPG). In addition, they will maintain the cell lines, animal resources, and equipment that support these functions. It is anticipated that all four projects of this PPG may potentially have need for the services provided by this Core facility. In addition, the Core will serve as a resourcefor members of the UT Southwestern Medical Center (UTSWMC) Comprehensive Cancer Center needing assistance with pharmacological assays. Since there are no other facilities here that can provide in-depth analysis of the behavior of novel small molecules in an in vivo setting, the creation of such a shared resource has the potential to impact the future development of translational cancer research at UTSWMC. The services provided by the Core facility will include: in vitro screening of compounds against a broad tumor panel;characterization of the metabolic stability of individual compounds in vitro and identification of metabolites as necessary;assessment of the solubility, plasma protein binding, and absorption characteristics of compounds in vitro;determination of the maximum in vivo tolerated dose and a preliminary assessment of toxicity;assessment of the distribution of compounds in small rodent models (pharmacokinetics);and development of mouse xenograft or other appropriate models for assessment of compound efficacy in vivo. The Pharmacology Core facility will work closely with PPG chemists to refine the structure of individual compounds so that characteristics that favor optimal efficacy in vivo will be maximized. There is an urgent need for new therapeutics to fight cancer, which in 2005 was responsible for over 500,000 deaths. The overall goal of this Program Project grant (PPG) is to discover and characterize synthetic, small molecule compounds that may be effective in the treatment of this disease. The Pharmacology Core facility will perform in vitro and in vivo measurements of compound concentration, toxicity, and efficacy in animal models. The overall goal of the Core is to guide chemical synthesis efforts of PPG projects in such a way that novel molecules with the best chance of clinical success in cancer patients are generated.
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