Membrane and Dye Efflux Assays to Detect and Characterize the Interaction of Drugs with ABC Transporters
Pp. 102-116 (15)
Eniko Ioja, Zoltan Nagy, Viktoria Juhasz, Judit Janossy, Krisztina Heredi-Szabo and Peter Krajcsi
The aim of this chapter is to describe the main in vitro assays used to predict the interaction of drugs
with ABC efflux transporters, to highlight their characteristics and to discuss their advantages and disadvantages.
In recent years, the number of synthesized compounds has increased dramatically as a result of advances in
combinatorial chemistry; consequently, early prediction of the interactions of drug-like compounds with efflux
transporters has garnered considerable attention. Moreover, transporter-related drug-drug interactions,
particularly in specific groups (children and the elderly), are of great concern. The withdrawal of marketed drugs
and the failure of drugs in the late clinical phase of drug research is often due to drug-drug interactions.
Furthermore, regulatory authorities require information on the potential for interactions to cause adverse effects: a
question that might be answered by in vitro assays even in the early stages of discovery. In vivo studies and cellbased
assays such as CaCo-2 monolayers have been elaborated, as well as quite expensive screening modes that
are primarily used for screening large numbers of compounds. By scaling the discussed in vitro assays up to
medium- or high-throughput screening modes, these assays can be efficiently used for the prediction of active
transport and transporter-mediated drug-drug interactions, and may be the most cost-effective approach to
transporter screening in drug discovery.
SOLVO Biotechnology, Central Hungarian Innovations Center.