Interaction of ABC Transporters with drugs

Abstract

ATP-binding cassette (ABC) proteins are causally related to the etiology of more than 25 human diseases. Selected members of the protein family play a role in drug disposition, drug resistance, and disease progression. The capability of ABC proteins to interact with small molecules has been well documented. An understanding of the mode of interaction of ABC proteins with drugs is an important aim for molecular and clinical pharmacology. The interaction of ABC proteins with drugs or drug candidates has been studied by structure-based and ligand-based approaches. In rare instances, a combination of both approaches has been attempted. Structure-based techniques rely on the availability of structural models of target ABC proteins at atomic resolution. Ligand-based studies infer information about drug-binding sites by complementarity between shape and properties of ligands on the one hand and binding sites on the other hand. These techniques are expected to lead to the identification of drug candidates for the treatment of those diseases, which are associated with ABC protein malfunction, but presently are not amenable to pharmacotherapy.