Phase 2 SBIR: Zebrafish Cytochrome P450 Assays for Assessing Drug Metabolism and

第 2 阶段 SBIR：斑马鱼细胞色素 P450 检测，用于评估药物代谢和

基本信息

批准号：
7848598
负责人：
Chunqi Li
金额：
$ 4.93万
依托单位：
PHYLONIX PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2010-08-27
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7848598
关键词：
Adverse effects Affect Animal Model Animals Automation Biological Assay Biological Availability CYP2C9 gene CYP2D6 gene CYP3A4 gene Collection Complex Cytochrome P450 Cytochromes Detection Drug Interactions Enzymes Evaluation Exhibits FDA approved Family Family member Fullerenes Genetic Goals Government Hepatic Hepatocyte Human In Vitro Lead Libraries Life Liquid substance Liver Mammals Metabolic Clearance Rate Metabolism Modeling Modification Mus Persons Pharmaceutical Preparations Pharmacologic Substance Phase Physiological Preclinical Drug Evaluation Preclinical Testing Process Rattus Reaction Reliance Research Safety Screening procedure Small Business Innovation Research Grant System Technology Testing Therapeutic Agents Toxic effect Transgenic Mice Transgenic Organisms Treatment Efficacy Zebrafish base clinically relevant cost drug candidate drug discovery drug metabolism drug use screening in vivo inhibitor/antagonist mouse model preclinical study public health relevance success

项目摘要

DESCRIPTION (provided by applicant): Cytochrome P450 (CYP) enzymes catalyze the majority of known drug metabolism and the bulk of these reactions occur in the liver. As a consequence, many clinically relevant drug-drug interactions are associated with inhibition and/or induction of a specific CYP enzyme. Modifications of CYP activities can have profound effects on therapeutic efficacy and can lead to life-threatening toxicity. In order to provide an early warning system for potential serious side effects, detection of specific CYPs responsible for drug metabolism and drug-drug interactions is a goal of all pre-clinical studies. An ideal CYP assay should be rapid, robust, reliable, reproducible, and amenable to automation in multiwell plate formats. This research will develop a microplate format high throughput whole zebrafish CYP functional assay for assessing drug metabolism and drug safety. Based on genetic and physiological similarity to humans, zebrafish show promise as an efficient, predictive animal model for assessing drug metabolism and drug safety. PUBLIC HEALTH RELEVANCE: Project Narrative The zebrafish assay will facilitate detection of specific cytochromes responsible for drug metabolism and drug-drug interactions, and provide an early warning system for potential serious side effects,

描述（由申请人提供）：细胞色素 P450 (CYP) 酶催化大多数已知的药物代谢，并且大部分这些反应发生在肝脏中。因此，许多临床相关的药物相互作用与特定 CYP 酶的抑制和/或诱导有关。 CYP 活性的改变会对治疗效果产生深远的影响，并可能导致危及生命的毒性。为了对潜在的严重副作用提供早期预警系统，检测负责药物代谢和药物间相互作用的特定 CYP 是所有临床前研究的目标。理想的 CYP 测定应该快速、稳健、可靠、可重复，并且适合多孔板形式的自动化。这项研究将开发一种微孔板形式的高通量全斑马鱼 CYP 功能测定，用于评估药物代谢和药物安全性。基于与人类的遗传和生理相似性，斑马鱼有望成为评估药物代谢和药物安全性的有效、预测性动物模型。公共健康相关性：项目叙述斑马鱼测定将有助于检测负责药物代谢和药物相互作用的特定细胞色素，并为潜在的严重副作用提供早期预警系统，