Core D: Animal Pharmacology & Models Core

核心 D：动物药理学

• 批准号: 10482429
• 负责人: Onur Cil
• 金额: $ 13.04万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10482429
• 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; 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 infections; Measurement; Measures; Meconium; Metabolic; Microsomes; Modeling; Mus; Names; Nephrolithiasis; Oral; Organ; Performance; Pharmaceutical Chemistry; Pharmacology; Preclinical Drug Development; Property; Pulmonary Inflammation; 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.

抽象的 这个新建立的核心D旨在推进新型的小分子疗法，用于胃肠道，肾脏， CF的内分泌和肺部表现，具有转化为诊所的潜力。实现这一目标 目标，核心D进行微粒体稳定性，动物药理学，功效和初步毒性 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，并在 Core C. Core D还提供了基本的资源和专业知识，以推动对CF器官的研究 表现和药物发现，包括建立CF疾病的实验动物模型和 提供转基因小鼠。核心D的拟议功能已在多个中成功执行 在当前奖励期内的项目，并正式建立核心D将使这些核心绩效 以更有效和有条理的方式发挥作用。核心D将促进的重要调查领域 包括CF便秘和相关疾病（幼虫和肠道阻塞综合征），CF- 相关的肠性高氧和肾石器症，CF相关糖尿病和肺部感染以及 炎。核心D将执行关键的动物实验，以测试已发现的上皮离子传输调节器 由CF核心中心（CF Core Center 表现形式并产生智力性，导致临床发展。