ATP-binding cassette sub-family G member 2 and ATP-binding cassette sub-family B member 1 (ABCG2 and ABCB1)

ATP-binding cassette sub-family G member 2 (ABCG2) and ATP-binding cassette sub-family B member 1 (ABCB1, also known as P-glycoprotein or P-gp) are two of the most critical efflux transporters in human physiology (UniProt P08183, Q9UNQ0). They are primarily expressed in the apical membranes of epithelial cells in the liver, kidneys, and intestines, as well as at blood-tissue barriers like the blood-brain barrier (BBB) and placenta (PMC7215456). Their primary biological function is the active, ATP-dependent transport of a wide range of xenobiotics and endogenous compounds out of cells, serving a protective role against toxicity. In oncology, these transporters are major contributors to multidrug resistance (MDR), as they efficiently efflux various chemotherapeutic agents, thereby reducing their intracellular concentration and efficacy (PubMed 16460407). Beyond cancer, ABCG2 is a key transporter for uric acid, and its dysfunction is strongly linked to hyperuricemia and gout (PMC4520404). Pharmacologically, these proteins are significant targets for inhibition to enhance the oral bioavailability and brain penetration of substrate drugs (MDPI 2024). However, targeting them presents challenges, including the risk of systemic toxicity and complex drug-drug interactions due to their broad substrate specificity.

Other names

Breast cancer resistance protein (BCRP)P-glycoprotein (P-gp)Multidrug resistance protein 1 (MDR1)CD243Mitoxantrone resistance-associated protein (MXR)Placenta-specific ATP-binding cassette transporter (ABCP)

These proteins function as ATP-dependent efflux pumps that utilize the energy from ATP hydrolysis to transport a diverse array of substrates across cellular membranes against their concentration gradients. Drugs targeting these transporters are typically inhibitors designed to block this efflux mechanism, thereby increasing the intracellular accumulation or systemic bioavailability of co-administered therapeutic agents.