Phamacology Core

药理学核心机构将负责实验的设计、执行和分析 解决抗癌的代谢稳定性、一般i//Vo毒性、药代动力学和体内功效 该计划项目补助金（PPG）产生的化合物。此外，他们将维持细胞系， 动物资源和支持这些功能的设备。预计这四个项目将 PPG可能需要该核心设施提供的服务。此外，核心将服务于 作为UT西南医学中心（UTSWMC）成员的资源， 中心需要药理学分析协助。因为这里没有其他设施可以 提供对新型小分子在体内环境中的行为的深入分析， 共享资源有可能影响转化癌症研究的未来发展， UTSWMC。核心设施提供的服务将包括： 广泛的肿瘤组;单个化合物的体外代谢稳定性的表征， 必要时鉴别代谢物;评估溶解度、血浆蛋白结合率，以及 化合物的体外吸收特性.体内最大耐受剂量和 毒性的初步评估;化合物在小型啮齿动物模型中分布的评估 （药代动力学）;以及开发用于评估 化合物在体内的功效。药理学核心设施将与PPG化学家密切合作， 因此，可以改变单个化合物的结构，使得有利于体内最佳功效的特性将最大化。 迫切需要新的治疗方法来对抗癌症，2005年癌症患者超过500，000人 死亡该计划项目补助金（PPG）的总体目标是发现和表征合成，小 分子化合物，可能是有效的治疗这种疾病。药理学核心设施 将在动物体内进行化合物浓度、毒性和功效的体外和体内测量 模型核心的总体目标是指导PPG项目的化学合成工作， 在癌症患者中产生最有可能临床成功的新分子。

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.