Understand if your compound inhibits the 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 inhibition 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.
2Draft FDA Guidance for Industry – In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies, October 2017.
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 |
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Probe Substrate | [3H]-Estradiol 17β-glucuronide (OATP1B1, OATP1B3) [3H]-PAH (OAT1) [3H]-Estrone 3-sulfate (OAT3, OAT4, OATP1A2, OATP2B1) [14C]-Metformin (OCT2, MATE1) (upon request for MATE2-K) [14C]-TEA (OCT1, MATE2-K) (upon request for MATE1) [3H]-cGMP (OAT2) [3H]-L-Carnitine (OCTN2) [3H]-Glycyl sarcosine (PEPT1, PEPT2) [3H]-Taurocholic acid (NTCP) |
Test Article Concentration | Single concentration (for batches of 6 compounds) OR 6 concentrations plus 0 µM (final test compound concentrations dependent on customer requirements) |
Time Point | Dependent on transporter |
Analysis Method | Radiochemical detection using scintillation counting |
Data Delivery | Percentage inhibition (single concentration) OR IC50 Written report available on request |
Related Services |
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P-gp |
Transporter | Substrate | Inhibitor | IC50 ± Standard Error (µM) |
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OATP1B1 | Estradiol 17β-glucuronide | Rifamycin | 0.67 ± 0.18 |
Cyclosporin A | 1.53 ± 0.22 | ||
OATP1B3 | Estradiol 17β-glucuronide | Rifampicin | 0.79 ± 0.11 |
Cyclosporin A | 0.96 ± 0.24 | ||
OAT1 | PAH | Probenecid | 16.6 ± 11.7 |
Diclofenac | 1.00 ± 0.36 | ||
OAT3 | Estrone 3-sulfate | Probenecid | 11.5 ± 2.64 |
Diclofenac | 18.7 ± 3.91 | ||
OCT1 | TEA | Verapamil | 7.59 ± 2.42 |
Quinidine | 30.5 ± 4.20 | ||
OCT2 | Metformin | Verapamil | 26.3 ± 2.42 |
Quinidine | 35.6 ± 2.03 | ||
MATE1 | Metformin | Cimetidine | 1.22 ± 0.09 |
Trimethoprim | 2.64 ± 0.27 | ||
MATE2-K | Metformin | Cimetidine | 3.34 ± 1.02 |
Trimethoprim | 0.35 ± 0.06 | ||
MATE1 | TEA | Cimetidine | 0.92 ± 0.10 |
Verapamil | 17.9 ± 3.88 | ||
MATE2-K | TEA | Cimetidine | 7.02 ± 5.27 |
Verapamil | 21.6 ± 1.79 | ||
OATP1A2 | Estrone 3-sulfate | Rifamycin SV | 3.44 ± 0.78 |
Ritonavir | 1.41 ± 0.77 | ||
OATP2B1 | Estrone 3-sulfate | Rifamycin SV | 2.72 ± 0.33 |
Ritonavir | 4.88 ± 0.85 | ||
Atorvastatin | 0.23 ± 0.08 | ||
OAT2 | cGMP | Indomethacin | 8.31 ± 0.62 |
Cimetidine | 239 ± 35.80 | ||
OAT4 | Estrone 3-sulfate | Losartan | 46.4 ± 3.12 |
Furosemide | 159 ± 25.70 | ||
OCTN2 | L-Carnitine | Meldonium | 32.3 ± 6.15 |
Verapamil | 111 ± 42.0 | ||
PEPT1 | Glycyl sarcosine | Losartan | 399 ± 62.55 |
Cefadroxil | 629 ± 157.50 | ||
PEPT2 | Glycyl sarcosine | Losartan | 34.9 ± 5.92 |
Cefadroxil | 22.6 ± 7.43 | ||
NTCP | Taurocholic acid | Pioglitazone | 10.2 ± 0.98 |
Cyclosporin A | 7.21 ± 1.75 |
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 Draft FDA Guidance for Industry – In Vitro Metabolism- and Transporter-Mediated Drug-Drug Interaction Studies, October 2017.
3 The European Medicines Agency (EMA) Guideline on the Investigation of Drug Interactions (Adopted 2012).
4 Zamek-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.