ABC (ATP-Binding Cassette) transporters are a superfamily of transmembrane proteins that use ATP hydrolysis to transport substrates \u2014 including drugs, metabolites, lipids, and ions \u2014 across biological membranes. They play a central role in drug absorption, distribution, metabolism, and excretion (ADME), making them critical targets in pharmaceutical development.<\/p>\n
The most pharmacologically relevant ABC transporters include P-glycoprotein (P-gp\/MDR1\/ABCB1), BCRP (ABCG2), MRP1 (ABCC1), MRP2 (ABCC2), MRP3 (ABCC3), MRP4 (ABCC4), and BSEP (ABCB11). These proteins are expressed in the intestine, liver, kidney, blood-brain barrier, and placenta, where they act as efflux pumps limiting drug bioavailability and mediating excretion.<\/p>\n
Regulatory agencies including the FDA and EMA require DDI assessment for new molecular entities that are substrates or inhibitors of key ABC transporters. Inhibition of P-gp or BCRP can significantly increase plasma concentrations of co-administered drugs, potentially causing toxicity. BSEP inhibition is specifically associated with drug-induced liver injury (DILI).<\/p>\n
The vesicle transport assay (inside-out membrane vesicles) and ATPase assay are the primary in vitro methods for characterizing ABC transporter interactions. Vesicle kits using human-derived membrane vesicles provide the most physiologically relevant data for regulatory submissions.<\/p>\n