Core D: Animal Pharmacology & Models Core

核心 D：动物药理学

• 批准号: 10001909
• 负责人: Onur Cil
• 金额: $ 11.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001909
• 关键词: Animal Experiments; Animal Model; Animals; Area; Award; Biological; Biological Availability; Blood; Clinic; Collection; Constipation; Data; Diabetes Mellitus; Digestive System Disorders; Disease; Disease model; Distal; Dose; Drug Kinetics; Endocrine; Enteral; Epithelial; Epithelium; Experimental Animal Model; Frequencies; Goals; Half-Life; High Pressure Liquid Chromatography; Human; Hyperoxaluria; Ileus; In Vitro; Intellectual Property; Intestinal Obstruction; Intravenous; Investigation; Ion Transport; Kidney; Knockout Mice; Liquid substance; Lung; Lung Inflammation; Lung infections; Measurement; Measures; Meconium; Metabolic; Microsomes; Modeling; Mus; Names; Nephrolithiasis; Oral; Organ; Performance; Pharmaceutical Chemistry; Pharmacology; Preclinical Drug Development; Property; Rattus; Research; Research Personnel; Resources; Rodent; Route; Serum; Surgical Equipment; Syndrome; Testing; Therapeutic; Tissue Harvesting; Tissues; Toxic effect; Transgenic Mice; Translations; Urine; Work; clinical development; commercialization; cystic fibrosis related diabetes; drug candidate; drug discovery; efficacy study; efficacy testing; epithelial Na+ channel; gastrointestinal; in vitro testing; in vivo; instrumentation; interest; intraperitoneal; lead candidate; liquid chromatography mass spectrometry; novel; novel therapeutics; overexpression; preclinical development; programs; ranpirnase; screening; small molecule; stool sample; subcutaneous; success; therapeutic candidate; tool

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.

摘要 这一新成立的Core D旨在推动胃肠道、肾脏、 CF的内分泌和肺部表现，并有可能转化为临床。要做到这一点 目的：核心D进行微球的稳定性、动物药理、疗效和初步毒性 对在核心A和B中确定并优化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，以推进对CF器官的研究 表现形式和药物发现，包括建立实验性的CF病动物模型，以及 提供转基因小鼠。核心D的拟议功能已在多个 在当前获奖期内的项目，并正式建立核心D将使这些项目的业绩 以更有效率和更有组织的方式运作。核心D将推动的重要调查领域 包括便秘和相关疾病(胎粪性肠梗阻和远端肠梗阻综合征)， 相关的肠源性高草酸尿和肾结石，与CF相关的糖尿病和肺部感染 发炎。Core 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 由CF核心中心提供，该中心在寻找治疗CF的新候选药物方面有着良好的记录 表现，并产生导致临床开发的知识产权。