Methotrexate transporters (MTX transporters)

Methotrexate transporters are a heterogeneous group of membrane proteins that regulate the movement of the antifolate drug methotrexate across biological membranes. This group includes ATP-binding cassette (ABC) transporters such as ABCG2 (Breast Cancer Resistance Protein) and ABCB1 (P-glycoprotein), which primarily function as efflux pumps to remove methotrexate from cells (UniProt Q9UNQ0, P08183). It also encompasses solute carrier (SLC) transporters like OATP1A2 and OATP1B3, which facilitate the uptake of methotrexate into tissues such as the liver and kidneys (PubMed: 21659486). These transporters are critical determinants of methotrexate pharmacokinetics, influencing its absorption, systemic distribution, and elimination. In oncology, the overexpression of efflux transporters like ABCG2 and ABCB1 is a major driver of multidrug resistance, allowing cancer cells to survive chemotherapy (PubMed: 15173115). In the treatment of autoimmune diseases like rheumatoid arthritis, genetic variations in these transporters, such as the ABCG2 c.421C>A polymorphism, are linked to variations in drug efficacy and the risk of toxicity (PubMed: 25614163). Furthermore, these proteins are significant sites for drug-drug interactions, as many other medications can inhibit or induce their activity, leading to potentially dangerous changes in methotrexate levels (FDA Drug Interaction Database). Overall, understanding the activity and genetic profile of these transporters is essential for optimizing methotrexate therapy and minimizing adverse outcomes like myelosuppression and hepatotoxicity.

Other names

ABCG2BCRPBreast cancer resistance proteinABCB1P-glycoproteinP-gpMDR1Multidrug resistance protein 1OATP1A2SLCO1A2Organic anion transporting polypeptide 1A2OATP1B3SLCO1B3Organic anion transporting polypeptide 1B3SLC19A1RFC1Reduced folate carrier 1SLC46A1PCFTProton-coupled folate transporterABCC1MRP1ABCC2MRP2ABCC3MRP3ABCC4MRP4Multidrug resistance-associated proteins

Mediation of ATP-dependent efflux and sodium-independent uptake of methotrexate and related antifolates across plasma membranes.