Understand if your compound is an in vitro substrate for the main hepatic Oatp uptake transporter of preclinical species, namely rat Oatp1b2, dog Oatp1b4 or Cynomolgus monkey Oatp1b1.
Preclinical species hepatic Oatp uptake 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.
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).
3Chu X 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
|Test Article Concentrations||Options:
- single concentration (typically, 1 µM), single timepoint for 7 compounds
- two concentrations (typically, 1 µM and 10µM), single timepoint for 3 compounds
- two concentrations (typically, 1 µM and 10µM), two timepoints for a single compound
|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|
Human SLC Transporter Substrate Identification
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 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.