Understand if your compound is a substrate for the main human SLC uptake transporters, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, OATP1A2, OATP2B1, OAT2, OAT4, OCTN2, PEPT1, PEPT2 or NTCP.
SLC uptake transporter substrate identification is within our portfolio of in vitro drug transporter screening services. Cyprotex deliver consistent, high quality data for either your early stage screening projects or your later stage regulatory studies according to FDA guidance and EMA guidance. Protocols can be adapted 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 controllong 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||Mammalian HEK293 cells transiently overexpressing a single transporter (OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, MATE2-K, OATP1A2, OATP2B1, OAT2, OAT4, OCTN2, PEPT1, PEPT2 or NTCP)
Control vector-transfected HEK293 cells
|Test Article Concentrations||Screening study - single concentration (typically, 1 µM), single timepoint for 7 compounds
Screening study - two concentrations (typically, 1 µM and 10µM), single timepoint for 3 compounds
Screening study - two concentrations (typically, 1 µM and 10µM), two timepoints for a 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, 2 min or 2 min 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 Schlessinger A et al., (2013) Molecular modeling and ligand docking for solute carrier (SLC) transporters. Curr Top Med Chem 13(7): 843-856.
2 FDA Guidance for Industry – In Vitro Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions (January 2020).
3 The European Medicines Agency (EMA) Guideline on the Investigation of Drug Interactions (Adopted 2012).
4Zamek-Gliszczynski M et al., (2018) Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance. Clin Pharmacol Ther 104(5): 890-899.
Learn more about permeability and drug transporters in our popular Everything you need to know about ADME guide.
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