Understand if your compound is an in vitro inhibitor of the main hepatic Oatp uptake transporter of preclinical species, namely rat Oatp1b2, dog Oatp1b4 or Cynomolgus monkey Oatp1b1.
Preclinical species hepatic Oatp 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.
It has become increasingly clear that there are significant differences between rodents, dog, monkey, and human in the substrate specificity, tissue distribution, and relative abundance of transporters. These differences complicate cross-species extrapolations, which is important when attempting to predict human pharmacokinetics (PK) of drug candidates and assess risk for drug-drug interactions (DDIs).
4Chu et al., (2013) Expert Opin Drug Metab Toxicol 9(3): 237-252.
|Test System||Mammalian HEK293 cells transiently overexpressing a single preclinical species transporter (rat Oatp1b2, dog Oatp1b4 or Cynomolgus monkey Oatp1b1)
Control vector-transfected HEK293 cells
|Probe Substrate||[3H]-Estradiol 17β-glucuronide|
|Test Article Concentrations||Single concentration (for batches of 6 compounds) OR 6 concentrations plus 0 µM (final test compound concentrations dependent on customer requirements)|
|Time Points||Dependent on transporter|
|Analysis Method||Radiochemical detection using scintillation counting|
|Data Delivery||Percentage inhibition (single concentration) OR
Human SLC Transporter Inhibition
|Transporter||Substrate||Inhibitor||IC50 ± Standard Error (µM)|
|Rat Oatp1b2||Estradiol 17β-glucuronide||Rifamycin SV||0.992 ± 0.188|
|Dog Oatp1b4||Estradiol 17β-glucuronide||Rifamycin SV||0.314 ± 0.0623|
|Cyno Oatp1b1||Estradiol 17β-glucuronide||Rifamycin SV||0.120 ± 0.0246|
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 Shitara Y et al., (2013) Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption. Biopharm Drug Dispos 34: 45-78.
3 Ufuk A et al., (2018) In Vitro-In Vivo Extrapolation of OATP1B-Mediated Drug-Drug Interactions in Cynomolgus Monkey. J Pharmacol Exp Ther 365(3): 688-699.
4 Chu X et al., (2013) Species differences in drug transporters and implications for translating preclinical findings to humans. Expert Opin Drug Metab Toxicol 9(3): 237-252.
Learn more about permeability and drug transporters in our popular Everything you need to know about ADME guide.