text: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
  The ATP-dependent drug efflux pump P-glycoprotein (P-gp) affects the absorption and disposition of many compounds. P-gp may also play role in clinically significant drug-drug interactions. Therefore, it is important to find potential substrates or inhibitors of P-gp early in the drug discovery process. To identify compounds that interact with this transporter, several P-gp assays were validated and compared by testing a set of 28 reference compounds, including inhibitors of cytochrome P450 3A4 (CYP3A4). The assays included in silico predictions, inhibition assays (based on cellular uptake of rhodamine-123 or calcein AM), and functional assays (ATPase activity assay and transcellular transport assay, the latter for a subset of compounds). In addition, species differences were studied in an indirect fluorescence indicator screening assay and test systems expressing porcine, mouse, or human P-gp. Our results suggest that several P-gp assays should be used in combination to classify compounds as substrates or inhibitors of P-gp. Recommendations are given on screening strategies which can be applied to different phases of the drug discovery and development process.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T1 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-N GENE-N GENE-N
entities.text: ATP-dependent drug efflux pump cytochrome P450 3A4 CYP3A4 P-gp ATPase P-gp P-gp P-glycoprotein ATP silico rhodamine-123 calcein AM P-gp P-gp P-gp P-glycoprotein P-gp