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 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.
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 | 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 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).
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.
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