High-throughput Prediction of Compound Tissue Distribution

复合组织分布的高通量预测

• 批准号: 7156127
• 负责人: CHARLES F SALLER
• 金额: $ 8.93万
• 依托单位: ANALYTICAL BIOLOGICAL SERVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2008-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7156127
• 关键词: adipose tissue; bioassay; biomimetics; computational biology; drug metabolism; drug screening /evaluation; fluorescent dye /probe; high throughput technology; liposomes; method development; pharmacokinetics; plasma; protein localization; tissues

DESCRIPTION (provided by applicant): Project Summary/Abstract: The aim of the proposed research is to develop tools for the prediction of the distribution of drug compounds in the human body. There is currently no experimental high throughput screening (HTS) method for determining compound tissue distribution. A drug compound's propensity to be taken up by different tissues and organs affects whether it will reach its action target, whether it will cause undesirable side-effects and hence, whether it will be clinically viable. A high-throughput in vitro method for predicting distribution of drug compounds in the human body would be an important addition to pre-clinical screening of new chemical entities (NCEs). This proposal is for the development of a novel method for the prediction for NCEs of the overall volume of distribution (Vss) and the relative distribution among tissues, consisting of a unique combination of simple fluorescent liposome-based in vitro screening assays and state-of-the-art computational models. The proposed method will be used in the pre-clinical evaluation of drug candidates to provide a standard and cost effective way to predict the overall distribution and specific tissue uptake of drug candidates. Project Narrative: Prediction of what will happen to a drug compound in the body is an important part of the drug development process. We are proposing to develop new tools for predicting where in the human body drug compounds will be distributed; this information will allow drug developers to determine early in the development cycle whether their drug candidates will reach their target and aid in their analysis of overall compound pharmacokinetics. Implementation of these tools will reduce the cost of drug development and accelerate the drug discovery process.

描述(由申请人提供)：项目摘要/摘要：拟议研究的目的是开发预测药物化合物在人体内分布的工具。目前还没有实验性的高通量筛选(HTS)方法来确定化合物的组织分布。一种药物化合物被不同组织和器官摄取的倾向影响着它是否达到其作用目标，是否会引起不良的副作用，从而影响它是否在临床上可行。一种预测药物化合物在人体内分布的高通量体外方法将是临床前筛选新化学实体(NCEs)的重要补充。这项建议是为了开发一种新的方法来预测NCEs的总体分布体积(VSS)和组织之间的相对分布，包括基于简单荧光脂质体的体外筛选分析和最先进的计算模型的独特组合。建议的方法将用于候选药物的临床前评估，为预测候选药物的整体分布和特定组织吸收提供一种标准和经济有效的方法。项目简介：预测药物化合物在体内会发生什么是药物开发过程的重要部分。我们正在提议开发新的工具来预测药物化合物将在人体内分布的位置；这些信息将使药物开发商能够在开发周期的早期确定他们的候选药物是否会达到他们的目标，并帮助他们分析化合物的整体药代动力学。这些工具的实施将降低药物开发的成本，并加快药物发现进程。