Core D: Animal Pharmacology & Models Core

摘要 这个新成立的核心D旨在推进胃肠道，肾脏， CF的内分泌和肺部表现，有可能转化为临床。实现这一 目的，核心D进行微粒体稳定性、动物药理学、有效性和初步毒性研究 对核心A和B中确定的候选药物进行表征和优先排序的研究， 核心C。核心D还提供必要的资源和专业知识，以推进CF器官的研究 包括建立CF疾病的实验动物模型，以及 提供转基因小鼠。核心D的拟议功能已成功地在多个 项目，并正式建立核心D将使这些性能 以更有效率和更有组织的方式运作。核心项目D将促进的重要调查领域 包括CF便秘和相关疾病（胎粪性肠梗阻和远端肠梗阻综合征），CF- 相关的肠道高尿酸和肾结石，CF相关的糖尿病和肺部感染， 炎症核心D将进行关键的动物实验，以测试发现的上皮离子转运调节剂 CF核心中心，该中心在确定CF的新型治疗候选药物方面有着良好的记录 临床表现，并产生导致临床开发的知识产权。

ABSTRACT This newly established Core D aims to advance novel small-molecule therapies for gastrointestinal, renal, endocrine and pulmonary manifestations of CF with the potential for translation into the clinic. To achieve this objective, Core D carries out microsomal stability, animal pharmacology, efficacy and preliminary toxicity studies to characterize and prioritize drug candidates that are identified in Cores A and B, and optimized in Core C. Core D also provides essential resources and expertise to advance research on CF organ manifestations and drug discovery that include establishing experimental animal models of CF disease, and providing transgenic mice. The proposed functions of Core D have been carried out successfully in multiple projects during the current award period, and formally establishing Core D will enable performance of these functions in a more efficient and organized manner. Important areas of investigation to be facilitated by Core D include CF constipation and related disorders (meconium ileus and distal intestinal obstruction syndrome), CF- related enteric hyperoxaluria and nephrolithiasis, CF-related diabetes mellitus and lung infections and inflammation. Core D will perform key animal experiments to test epithelial ion transport modulators discovered by the CF Core Center, which has a track record of identifying novel therapeutic candidates for CF manifestations, and generating intellectual property leading to clinical development.