Medicinal Chemistry Core

药物化学核心

基本信息

批准号：
10649658
负责人：
ROBERT H MACH
金额：
$ 131.6万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-24 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10649658
关键词：
ABCB1 gene Affinity Alzheimer&apos s Disease Basic Science Binding Binding Sites Biological Assay Brain Collaborations Computer Models Development Docking Evaluation Filament Frontotemporal Dementia Goals High Pressure Liquid Chromatography Image In Vitro Individual Institution Lead Ligands Measurement Measures Methods Monitor Multiple System Atrophy Octanols Paralysed Parkinson Disease Partition Coefficient Patients Pennsylvania Pharmaceutical Chemistry Positron-Emission Tomography Property Protein Chemistry Radiochemistry Radiolabeled Research Research Contracts Research Personnel Research Project Grants Series Site Specificity Structure Structure-Activity Relationship Tauopathies Teleconferences Testing Tissues Universities Washington Water alpha synuclein analog brain tissue clinical imaging high throughput screening imaging agent imaging study in silico in vitro Assay in vivo innovation lipophilicity member molecular dynamics multidisciplinary novel radioligand radiotracer scale up screening small molecule structural biology targeted agent tau Proteins uptake

项目摘要

MEDICINAL CHEMISTRY AND RADIOCHEMISTRY CORE ABSTRACT The Medicinal Chemistry and Radiochemistry (MCRC) Core represents the central hub of activity of this U19 Center. The initial focus of the MCRC Core is the use of novel in silico methods for the identification of lead compounds for PET radiotracer development for alpha synuclein (Asyn) and 4R tau. This approach to lead compound identification is highly innovative since it has never been applied prior to this in the field of PET radiotracer development. Once in silico hits have been confirmed as true lead compounds from the radioligand binding studies conducted in Projects 1 and 2, the MCRC Core will be responsible for conducting structure-activity relationship (SAR) studies to identify compounds having the appropriate properties for radiolabeling and additional in vitro and in vivo characterization. The radiolabeling studies will be conducted by the radiochemistry component of the MCRC Core. There are four different sites involved in the MCRC Core, the University of Pennsylvania, Washington University-St. Louis, the University of Pittsburgh, and the contract research organization, MedChem Imaging. The Core Co-Directors are Drs. Robert H. Mach and E. James Petersson of Penn; each site will also have a site P.I. (C. Mathis, Pitt; Z. Tu, Wash U; Neil Vasdev, MedChem Imaging). The site P.I.s will serve as members of the Executive Steering Committee, who will meet via video teleconference on a bi-weekly basis. The goal of the Executive Steering Committee is to monitor progress of the in silico screening methods and in vitro binding studies, and the determination of which group should be assigned the resultant SAR studies on the true lead compounds. Another goal of the MCRC Core is to conduct an in vitro assay to determine if promising compounds are substrates for P-glycoprotein. A final function of the MCRC Core is to conduct scale-up synthesis of precursors and standards required for the imaging studies conducted by the Clinical Imaging Core.

药物化学和放射化学核心摘要药物化学和放射化学（MCRC）核心代表了活动的中心枢纽 U19中心。 MCRC核心的初始重点是在硅方法中使用小说用于α突触核蛋白（ASYN）和4R tau的宠物放射性示例发育的铅化合物的铅化合物。这铅复合识别的方法具有很高的创新性，因为它在此之前从未应用在宠物放射性示例发育领域。一旦进入计算机击中，已被确认为真实的铅来自项目1和2进行的放射性结合研究的化合物，MCRC核心将是负责进行结构活动关系（SAR）研究，以识别具有适当的放射性标记和额外体外和体内表征的特性。这放射性标记研究将由MCRC核心的放射化学成分进行。 MCRC核心，宾夕法尼亚大学，华盛顿有四个不同的地点大学圣。路易斯，匹兹堡大学和Medchem合同研究组织成像。核心联合导演是Drs。罗伯特·H·马赫（Robert H. Mach）和宾夕法尼亚州的詹姆斯·彼得森（E. James Petersson）；每个站点还将有一个网站P.I. （C. Mathis，Pitt; Z. tu，Wash U； Neil Vasdev，Medchem成像）。网站P.I.S 将担任执行指导委员会的成员，他们将通过视频电话会议开会每两周。执行指导委员会的目标是监视硅的进度筛选方法和体外结合研究，以及应分配哪个组的确定最终的SAR研究对真实铅化合物。 MCRC核心的另一个目标是进行在体外测定中确定有希望的化合物是否是P-糖蛋白的底物。最终功能 MCRC核心是进行成像所需的前体和标准标准的规模合成通过临床成像核心进行的研究。