Membrane drug transporters (SLC/ABC Transporters)

Membrane drug transporters are a diverse group of proteins, primarily from the Solute Carrier (SLC) and ATP-binding cassette (ABC) families, that regulate the movement of drugs and endogenous molecules across cellular membranes [1, 2]. Key members such as Solute carrier organic anion transporter family member 1B1 (OATP1B1) and ATP-binding cassette sub-family G member 2 (BCRP) are essential for the hepatic uptake and systemic efflux of various medications [3]. These transporters are major determinants of a drug's pharmacokinetic profile, influencing its absorption, distribution, and elimination [3]. Genetic variations in these transporters, such as the SLCO1B1*5 allele, are linked to altered drug responses and increased risks of toxicity, notably statin-induced myopathy [1, 5]. In clinical practice, these proteins are frequently involved in drug-drug interactions (DDIs) when one drug inhibits the transport of another, leading to potentially dangerous increases in plasma concentration [3]. Regulatory agencies like the FDA and EMA require the evaluation of new molecular entities as substrates or inhibitors of these transporters to ensure patient safety [3]. Beyond pharmacology, they play vital roles in physiological homeostasis by transporting bile acids, bilirubin, and uric acid [1, 2]. BCRP, in particular, is associated with multidrug resistance in cancer cells, where it pumps chemotherapeutic agents out of the cell, reducing treatment efficacy [2]. Endogenous biomarkers like coproporphyrin I and III are increasingly used to assess the in vivo activity of OATP transporters in early clinical trials [4].

Other names

ADME transportersClinically relevant drug transportersXenobiotic transportersSLC and ABC transportersDrug-drug interaction (DDI) transporters

Inhibition or induction of membrane-bound transport proteins, which alters the transmembrane flux of substrate drugs and endogenous compounds, thereby modifying their systemic exposure and tissue distribution [3].