Understand if your compound and/or metabolite is a substrate for the human efflux transporters, MRP2, MRP3 or MRP4.
MRP efflux transporter substrate identification is within our portfolio of in vitro drug transporter services. Cyprotex deliver consistent, high quality data with the flexibility to adapt protocols based on specific customer requirements.
Membrane transporters can have clinically relevant effects on the pharmacokinetics and pharmacodynamics of a drug in various organs and tissues by controlling its absorption, distribution and elimination.
2FDA Guidance for Industry – In Vitro Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions (January 2020)
|Test System||Sf9 insect cell-derived or mammalian (HEK293) cell-derived inside-out membrane vesicles overexpressing a single transporter (MRP2, MRP3 or MRP4) incubated in the presence of ATP and AMP (absence of ATP)|
|Test Article Concentrations||Screening study – single concentration (typically 1 µM), single timepoint for 7 compounds
Screening study – two concentrations (typically 1 and 10 µM), single timepoint for 3 compounds
Screening study – two concentrations (typically 1 and 10 µM), two timepoints for single compound
Regulatory study - typically 1, 10, 50 and 100 µM (depending on customer requirements) plus inhibition at two substrate concentrations (two timepoints)
|Time Points||Typically, 10 min or 10 and 20 min (depending on customer requirements)|
|Analysis Method||MicroBeta® scintillation counter (radiolabelled substrates)
LC-MS/MS analysis (non-radiolabelled substrates)
|Data Delivery||Cellular uptake and fold accumulation
Written report available on request
1 Zamek-Gliszczynski MJ et al., (2018) Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance. Clin Pharmacol Ther 104(5): 890-899
2 FDA Guidance for Industry – In Vitro Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions (January 2020)
Learn more about permeability and drug transporters in our popular Everything you need to know about ADME guide.