Preclinical Species Hepatic Oatp Substrate Identification

Preclinical species hepatic Oatp uptake transporter substrate identification is within our portfolio of in vitro drug transporter services. Cyprotex delivers consistent, high quality data in line with our published transporter strategy review ,for either your early stage screening projects or your later stage regulatory studies.

Identifying potential substrates of preclinical species hepatic uptake transporters in vitro:

• The SLC (solute carrier) super family of transporter proteins, transport a wide range of different solutes across biological membranes using diverse energy coupling mechanisms¹.
• One of the most important human SLC transporters expressed in human liver is OATP1B1 which is responsible for the hepatic uptake and rate-determining elimination of a wide range of endogenous compounds and drugs that are substrates².
• Species differences in drug transporters with regard to their tissue distribution, expression levels and substrate specificity can be problematic for preclinical cross-species extrapolation of drug disposition (clearance) and DDI potential to human.
• The use of in vitro cell test systems that each overexpress the major hepatic Oatp transporter of preclinical species (Oatp1b2, Oatp1b4 or Oatp1b1 for rat, dog or Cynomolgus monkey, respectively) may be useful towards understanding whether a molecule is a substrate of a hepatic active uptake transporter in those species. Such knowledge may assist in the interpretation of any observed liver accumulation in vivo, or help towards qualitatively understanding an underprediction of in vivo hepatic clearance from in vitro microsomal clearance data for that preclinical species.
• Cyprotex’s preclinical species hepatic Oatp transporter substrate identification assay determines if your compound is a substrate of key preclinical species transporters.

_{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}