ABCG2, more commonly referred to as BCRP (Breast Cancer Resistance Protein), is an efflux transporter that serves two major drug transport functions. Firstly, it restricts the distribution of its substrates into organs such as the brain, testes, placenta, and across the gastrointestinal tract (GIT). Secondly, it eliminates its substrates from excretory organs, mediating both biliary and renal excretion, and occasionally direct gut secretion. Although less well studied than e.g. MDR1, BCRP is generally co-expressed with MDR1, and shares many of its substrates, inhibitors and inducers. Of its known substrates, rosuvastatin has been implicated in DDI, especially with perpetrator drugs that also inhibit OATPs (e.g. cyclosporine). It is probable that a synergy exists between the action of BCRP, MDR1, and the drug-metabolizing enzyme CYP3A4, particularly in the GIT.
BCRP is included in the list of important drug transporters that both the FDA and EMA consider necessary to investigate regarding liabilities for NCEs. Drugs whose ADME, and bioavailability in particular, is influenced by BCRP may require clinical investigation to reveal a potential DDI with potent clinical BCRP inhibitors. For instance, since the GIT absorption of rosuvastatin is modulated by BCRP, it may be necessary to study the impact of BCRP inhibitors on the oral absorption of rosuvastatin. Because of the potential synergy between BCRP, CYP3A4, and MDR1, a clinical investigation examining the contribution of both drug transporters and enzymes to drug ADME may be necessary.
P-gp & BCRP inhibitor
Elacridaris a prototypical BCRP inhibitor which inhibits the Bcrp1-mediated transport. Learn More
Ko 143 is potent and selective inhibitor of breast cancer resistance protein multidrug transporter (BCRP) with an EC90 value of 26 nM. Learn More
KS-176 is a potent and selective inhibitor of the breast cancer resistance protein (BCRP) multidrug transporter (IC50 values are 0.59 and 1.39 uM in Pheo A and Hoechst 33342 assays respectively). Learn More
YHO-13177 is a potent and specific inhibitor of breast cancer resistance protein (BCRP/ABCG2). Learn More
P-gp/BCRP dual inhibitor
FD 12-9 is a flavonoid dimer, acts as a dual inhibitor of P-gp and BCRP, with EC50s of 285 nM and 0.9 nM, respectively. Anti-glioblastoma activity. Learn More