Transporter assays as useful in vitro tools in drug discovery and development

Drug transporters are transmembrane proteins that facilitate the transfer of substances in and out of cells and play a substantial role in drug absorption, distribution and elimination. During the drug discovery and development phases, in vitro assays are important tools to identify substrates and inhibitors of transporters.

This article provides an overview of in vitro transporter assays, discussing their advantages, limitations, and sources of variability. Membrane-based assays take advantage of the location of efflux transporters for measurements of drug interactions. Cell-based systems are functional transporter assays that measure the passage of drugs across cell membranes and transporter proteins.

Use of optimized and validated in vitro transporter assays during drug discovery and development leads to a greater confidence in their results in determining whether a new compound is a substrate or inhibitor. The concept of transporter method suitability provides a general scheme to improve predictability and reduce variability of the in vitro assays by incorporating assay validation, acceptance criteria, and probe substrates and inhibitors. Such a scheme can potentially improve assay reproducibility and allow in vitro transporter assays to aid in defining a test compound as a substrate or inhibitor of efflux and uptake transporters.