Novel small-molecule therapies for CF

CF 的新型小分子疗法

基本信息

批准号：
10001904
负责人：
Peter Michael Haggie
金额：
$ 58.47万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/10001904
关键词：
Animals Area Biological Assay California Cell model Cells Cellular Assay Chemistry Clinic Collaborations Constipation Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Defect Development Disease Drug Kinetics Drug Screening Drug Targeting Enteral Evaluation Fostering Funding GTP-Binding Protein alpha Subunits, Gs Goals Human Hyperoxaluria Ileus Infrastructure Institution Intellectual Property Investigation Ion Transport Ions Kidney Kidney Diseases Laboratories Legal patent Licensing Meconium Microfluidics Modeling Mutation Nephrolithiasis Pathway interactions Patients Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacology Pilot Projects Population Recording of previous events Research Research Contracts Research Personnel Resources Running SLC26A3 gene San Francisco Testing Therapeutic Translating Translational Research Translations Universities Validation Work base clinically relevant cost drug candidate drug development drug discovery drug testing effective therapy experience gastrointestinal high throughput screening inhibitor/antagonist innovation loss of function mutant novel programs ranpirnase small molecule targeted treatment therapy development

项目摘要

ABSTRACT This is a proposal to continue the Cystic Fibrosis (CF) Research and Translation Center at the University of California, San Francisco and collaborating institutions. The focus of our Center remains the discovery and advancement of novel small-molecule therapies for CF. The original proposal 15 years ago followed from 5 years of work establishing a unique academic drug discovery program in the laboratories of Dr. Verkman and collaborators to identify and characterize small-molecule modulators of CFTR. The proposed Center will fund four scientific Cores and an administrative Core to support the activities of 2 Pilot Projects and at least 22 CF- related projects. The Core directors are experienced CF investigators with recognized expertise in their areas of investigation and a history of productive collaboration. The Cores include: High-Throughput Screening (Core A, Alan Verkman, Director), Assays & Cell Models (Core B, Peter Haggie, Director), Chemistry (Core C, Mark Kurth (UC Davis) and Marc Anderson (San Francisco State University), co-Directors), and Animal Pharmacology & Models (Core D, Onur Cil, Director). Major focuses of projects utilizing the Cores include development of therapies for the `remaining 10%' of CF subjects that are not benefitted by available CFTR modulators, which include tailored modulators for rare and difficult-to-treat CFTR mutants, and mutation- agnostic therapies such as SLC26A4 (pendrin) inhibitors and SLC26A9 modulators; and therapies targeting gastrointestinal and renal complications of CF, such as SLC26A3 (DRA) inhibitors for CF constipation and enteric hyperoxaluria, and SLC26A6 (PAT-1) inhibitors for CF constipation and meconium ileus. The goal of the research to be enhanced by the Center remains the development of novel small-molecule therapies for CF that can be translated into the clinic.

抽象的这是继续在大学的囊性纤维化（CF）研究与翻译中心的提议加利福尼亚，旧金山和合作机构。我们中心的重点仍然是发现，新型小分子疗法的进步。 15年前的原始提议随后是5 多年的工作，在Verkman博士的实验室中建立独特的学术药物发现计划和合作者识别和表征CFTR的小分子调节器。拟议的中心将资助四个科学核心和一个行政核心，以支持2个试点项目的活动，至少22 cf- 相关项目。核心主管是经验丰富的CF调查人员，在其地区具有公认的专业知识调查和富有成效的合作历史。核心包括：高通量筛选（核心 A，Alan Verkman，导演），分析和细胞模型（Core B，Peter Haggie，董事），化学（Core C，Mark，Mark 库尔斯（加州大学戴维斯分校）和马克·安德森（Marc Anderson）（旧金山州立大学），联合导演）和动物药理学与模型（核心D，Onur CIL，主任）。利用核心的项目重点包括开发未从可用CFTR受益的“剩余10％” CF受试者的疗法开发调节器，其中包括针对稀有和难以处理的CFTR突变体的量身定制调节剂，以及突变 - 不可知论疗法，例如SLC26A4（Pendrin）抑制剂和SLC26A9调节剂；和靶向疗法 CF的胃肠道和肾脏并发症，例如SLC26A3（DRA）抑制剂，用于CF便秘和用于CF便秘和幼虫的肠肠尿和SLC26A6（PAT-1）抑制剂。目标该中心要增强的研究仍然是CF的新型小分子疗法的发展可以将其转化为诊所。