A variety of uptake and efflux transporters are located at the membranes of organs, such as the gastrointestinal tract, brain, liver, or kidneys, and impact the absorption and distribution of compounds, as well as their safety and efficacy. The prediction of intestinal absorption is crucial in the design and selection of a drug candidate, as poor permeability can lead to inadequate absorption and consequently to insufficient drug exposure at the target after oral dosing. Additionally, transporters may contribute to eliminating compounds via renal or biliary excretion or intestinal secretion. Consequently, the inhibition or induction of transporters can be the cause of drug–drug interactions.
In our transporter laboratory, we offer a range of in vitro assays that are consistent with industry standards to assess the permeability and transporter interaction of your compounds. The classical, bidirectional Caco-2 assay uses a differentiated and polarized colon carcinoma cell line to determine both active and passive membrane permeation. The permeability of a test compound through the cellular monolayer is assessed in both directions: apical to basal and basal to apical. The resulting efflux ratio informs about the involvement of active efflux or uptake transporters. Our Caco-2 assay can be implemented early in your screening cascade, since a high throughput is ensured by a fully automated robotic platform. Depending on your needs, the involvement of, for instance, permeability-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) can be investigated via incubation in the absence or presence of selective P-gp or BCRP inhibitors. Our portfolio further includes assays in MDCK cells showing a P-gp or BCRP overexpression.
We understand that every drug discovery project is unique, which is why our experienced scientists support you from choice of the optimal assay design up to the interpretation of results in the project context. If you are looking for reliable transporter assay services to support your drug discovery efforts, contact us today to learn more about our services and how we can help you achieve your research goals.