Breast Cancer Resistance Protein: Structure, Localization, Functions, Significance for Rational Pharmacotherapy

Abstract

INTRODUCTION: Currently, investigation of efflux transport systems of an organism is an important scientific and practical task permitting to more deeply investigate the pharmacokinetics of medical drugs and to optimize pharmacotherapy of a number of diseases. The super family of ABC transporters plays a significant role in transport of biobiotics, the processes of absorption, distribution and excretion of medical drugs from an organism, in realization of undesired drug-drug interactions and development of pharmacoresistance. An important representative of this super family is breast cancer resistance protein (BCRP).

AIM: Systematization of the data on BCRP structure, localization, functions, substrates and modulators of its activity.

This literature review presents modern data on the molecular and spatial structure of BCRP, its localization in the cell, in organs and tissues. The data from studies of the functions of BCRP in an organism, of its role in the development of undesired drug-drug interactions at different stages of pharmacokinetics are summarized. An up-to-date list of medicinal drugs that are substrates and inhibitors of BCRP is given. Modern approaches to testing medical drugs for belonging to BCRP substrates or modulators of its activity are disclosed.

CONCLUSION: The significance of BCRP consists in the existence of a wide range of drugs that are its substrates or modulators of its activity. Upon that, of increasing significance is the investigation both of new and long-known medicinal substances for their belonging to substrates, inducers or inhibitors of breast cancer resistance protein, in order to increase the effectiveness of pharmacotherapy and reduce the risk of undesired drug interactions. Search for non-drug substrates and modulators of BCRP activity permits to obtain new markers for conducting effective studies of safe pharmacokinetics both in vitro and in vivo.

Keywords

breast cancer resistance protein / ABC transporters / drug resistance / drug-drug interactions / structure / inducers / inhibitors

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