Structure and function of BCRP, a broad specificity transporter of xenobiotics and endobiotics

Abstract

The discovery and characterization of breast cancer resistance protein (BCRP) as an efflux transporter conferring multidrug resistance has set off a remarkable trajectory in the understanding of its role in physiology and disease. While the relevance in drug resistance and general pharmacokinetic properties quickly became apparent, the lack of a characteristic phenotype in genetically impaired animals and humans cast doubt on the physiological importance of this ATP-binding cassette family member, similarly to fellow multidrug transporters, despite well-known endogenous substrates. Later, high-performance genetic analyses and fine resolution tissue expression data forayed into unexpected territories concerning BCRP relevance, and ultimately, the rise of quantitative proteomics allows putting observed interactions into absolute frameworks for modeling and insight into interindividual and species differences. This overview summarizes existing knowledge on the BCRP transporter on molecular, tissue and system level, both in physiology and disease, and describes a selection of experimental procedures that are the most widely applied for the identification and characterization of substrate and inhibitor-type interactions.

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…BRCP transporters align with P-gp and MRP proteins in efflux function [100]. BCRP is present in both the small and the large intestine and its expression does not vary significantly per location [101].…”

Modulating the function of ATP-binding cassette subfamily G member 2 (ABCG2) with inhibitor cabozantinib

“…ABCG2 docking grid was generated by selecting significant residues (Asn 387 , Gln 398 , Thr 402 , Arg 482 , Asn 629 , Thr 642 and Tyr 645 ) at the centroid of the transmembrane domain as centroid [6,43]. Glide XP docking protocol (Schrödinger, LLC, New York, NY) was followed to dock all prepared 100 cabozantinib conformations into ABCG2.…”

Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins

“…The highest expression of BCRP is detected in placental tissue, specifically on apical syncytiotrophoblast membranes. Other tissues with high expression of BCRP include the blood-brain barrier, testis, and lactating mammary tissue (Jani et al, 2014). In the kidney, BCRP localizes to apical membranes of proximal tubule epithelial cells; however, its level of expression is less compared with the intestine and liver (Mao and Unadkat, 2015).…”