ATP-binding cassette sub-family B member 1 (P-gp) and ATP-binding cassette sub-family G member 2 (BCRP) (P-gp / BCRP)

P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2) are two of the most significant ATP-binding cassette (ABC) efflux transporters involved in drug disposition and multidrug resistance [2, 15]. They are strategically expressed at physiological barriers such as the blood-brain barrier (BBB), the intestinal epithelium, and the canalicular membrane of hepatocytes, where they function as a "cooperative team of gatekeepers" to limit the entry of xenobiotics and therapeutic agents into sensitive tissues [4, 6]. These transporters have broad and overlapping substrate specificities, encompassing a wide range of chemotherapeutics, antivirals, and cardiovascular drugs [1, 23]. In oncology, their overexpression in tumor cells is a major mechanism of multidrug resistance (MDR), as they actively pump drugs out of the cell, thereby reducing therapeutic efficacy [2, 22]. Because of their functional redundancy, particularly at the BBB, dual inhibition of both P-gp and BCRP is often necessary to achieve significant increases in the tissue penetration or oral bioavailability of shared substrates [10, 12]. Consequently, they are critical targets in drug development for overcoming resistance and optimizing drug delivery to the central nervous system [9, 23].

Other names

ABCB1ABCG2MDR1CD243MXRABCPCDw338Permeability glycoproteinBreast Cancer Resistance ProteinMultidrug resistance protein 1

ATP-dependent efflux of substrates across the plasma membrane against a concentration gradient.