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

描述(申请人提供)：细胞色素P450(CYP)酶催化大多数已知的药物代谢，这些反应大部分发生在肝脏。因此，许多临床上相关的药物-药物相互作用与抑制和/或诱导特定的CYP酶有关。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。为了提供一个潜在的严重副作用的早期预警系统，检测负责药物代谢和药物-药物相互作用的特定的细胞周期蛋白是所有临床前研究的目标。理想的CYP测定应快速、可靠、可靠、重复性好，并能以多孔板的形式实现自动化。本研究将建立一种微板式高通量全斑马鱼细胞色素P450功能分析方法，用于评价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、可预测的动物模型。公共卫生相关性：项目简介斑马鱼化验将有助于检测负责药物新陈代谢和药物间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，

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,