DEVELOPMENT OF CACO-2 CELLS EXPRESSING CYTOCHROME P450

我们建议评估表达人细胞色素的可行性。 Caco-2人肠上皮细胞中P450(CYP)cDNA的表达 研究药物/异种生物吸收和运输的系统。表达式 研究将使用CYP2A6作为方便和适当的 模型酶，然后延伸到细胞色素P450，主要的细胞色素P450 人的肠上皮细胞。转基因细胞在体外培养中的适应性 对异种生物运输的研究也将进行评估。总目标 是开发表达人细胞色素的Caco-2细胞衍生物 在体内发现P450，以便在肠道内建立更好的 药物转运/代谢的体外模型系统及其检测 潜在的治疗相关药物-药物或药物-营养素 互动。 建议的商业应用：一种改进的体外模型系统 研究药物代谢和摄取。一个有用的系统来帮助选择 应该开发候选药物。

We propose to evaluate the feasibility of expressing human cytochrome P450 (CYP) cDNAs in Caco-2 human intestinal epithelial cells, a model system for the study of drug/xenobiotic uptake and transport. Expression studies will be conducted using CYP2A6 as a convenient and appropriate model enzyme and then extended to CYP3A4, the major cytochrome P450 in human intestinal epithelium. The suitability of transfected cells for studies of xenobiotic transport will also be evaluated. The overall goal is to develop Caco-2 cell derivatives which express the human cytochrome P450s found in the intestine in vivo in order to establish a better in vitro model system for drug transport / metabolism and for detecting the potential therapeutically relevant drug-drug or drug-nutrient interactions. PROPOSED COMMERCIAL APPLICATION: An improved in vitro model system to study drug metabolism and uptake. A useful system to help choose which drug candidates should be developed.