Novel small-molecule therapies for CF

CF 的新型小分子疗法

• 批准号: 6987671
• 负责人: ALAN S VERKMAN
• 金额: $ 110.33万
• 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: 2005-09-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6987671
• 关键词: biomedical facility; chloride channels; clinical research; cystic fibrosis; drug discovery /isolation; metabolism disorder chemotherapy; small molecule

This is a proposal to establish a Cystic Fibrosis (CF) Research and Translational Core Center at the University of California, San Francisco and collaborating institutions. The focus of the Core Center is to facilitate the discovery and evaluation of novel small-molecule therapies for CF. This proposal is the culmination of 5 years of work establishing a unique academic drug discovery program to identify and characterize inhibitors of CFTR and activators of CF-causing CFTR mutants. The proposed Core Center will fund 7 Cores that will support the activities of 2 Pilot Projects and at least a dozen ongoing CF-related projects. The Core directors and users are in most cases senior CF investigators with recognized expertise in their areas of investigation and a history of productive collaboration. The Cores include: high-throughput screening, clinical resources, cell models, animal models, organic/medicinal chemistry, CFTR biochemistry, and electrophysiology. The principal projects to utilize the Core include the discovery and evaluation of small-molecules: to activate CF-causing CFTR mutants such as deltaF508 and G551D (for treatment of the underlying defect in CF); to inhibit CFTR (for development of CF animal models), to enhance non-viral gene delivery (for CF gene therapy), to kill bacteria (for CF antimicrobial therapy), and to reduce airway surface fluid viscosity (for therapy of CF lung disease). The goal of the research to be enhanced by the Core Center is to develop new small-molecules therapies for CF that can be translated into the clinic.

这是在加利福尼亚大学，旧金山和合作机构建立囊性纤维化（CF）研究和转化核心中心的建议。核心中心的重点是促进对CF的新型小分子疗法的发现和评估。该提案是建立独特的学术药物发现计划的5年工作的高潮，以识别和表征CFTR的抑制剂和CF引起CFTR突变体的激活剂。拟议的核心中心将资助7个核心，这些核心将支持2个试点项目的活动和至少十二个与CF相关的项目。在大多数情况下，核心董事和用户是高级CF调查人员，在调查领域和生产性合作史上具有公认的专业知识。核心包括：高通量筛查，临床资源，细胞模型，动物模型，有机/药物化学，CFTR生物化学和电生理学。利用核心的主要项目包括对小分子的发现和评估：激活CF引起CF的CFTR突变体，例如Deltaf508和G551D（用于治疗CF中的基本缺陷）；为了抑制CFTR（用于开发CF动物模型），以增强非病毒基因递送（用于CF基因治疗），杀死细菌（用于CF抗菌治疗）以及降低气道表面流体粘度（用于CF肺病的治疗）。核心中心增强研究的目的是开发可转化为诊所的新型CF小分子疗法。