Uptake Transporters

• Substrate and inhibition assays
• Using human embryonic kidney (HEK293) cells transiently transfected with a single human transporter

A family of solute carriers (SLC) is an important group of membrane transporters involved in drug absorption, distribution and elimination. Regulatory authorities (EMA, FDA) recommend investigating the potential roles of SLC superfamily members OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1 and MATE2 for transporter-mediated drug-drug interactions (DDI), by evaluating whether the new drug candidate is a substrate (potential DDI victim) or an inhibitor (potential DDI perpetrator) towards drug transporters. In addition, EMA suggests also considering investigation of OCT1, whenever in vitro and in vivo findings suggest its involvement in DDI to be anticipated.

In substrate assays the active uptake of the test compound into cells is measured directly, while transporter inhibition is evaluated by measuring the cellular uptake of a probe substrate into cells in the presence and absence of the test compound. Both assays can be tailored for screening using 1-2 concentrations or to fulfill regulatory guidelines using a more comprehensive study set-up. Assays are conducted with human embryonic kidney (HEK293) cells transiently transfected with a single human transporter and LC/MS/MS is used as an analytical tool.