Organic cation transporters and multidrug and toxin extrusion proteins (OCT/MATE)

The Organic Cation Transporters (OCTs) and Multidrug and Toxin Extrusion (MATE) proteins represent a functionally integrated system responsible for the disposition of organic cations (Motohashi & Inui, 2013, PMID: 23588310). OCT1 (SLC22A1), OCT2 (SLC22A2), and OCT3 (SLC22A3) primarily facilitate the uptake of small organic cations from the blood into the liver and kidneys (UniProt O15245, O15244). Subsequently, MATE1 (SLC47A1) and MATE2-K (SLC47A2) act as apical efflux transporters, moving these cations into the bile or urine using an oppositely directed proton gradient (UniProt Q96FL8, Q86VL8). This pathway is the primary route of elimination for several clinically significant drugs, including the first-line diabetes medication metformin and the platinum-based chemotherapeutic cisplatin (Hillgren et al., 2013, PMID: 23686336). Because these transporters share many substrates and inhibitors, they are frequently evaluated together during drug development to predict potential drug-drug interactions as per FDA and EMA guidelines. Inhibition of the OCT/MATE pathway can lead to significant clinical consequences, such as reduced renal clearance of metformin or increased intracellular accumulation of cisplatin, which exacerbates nephrotoxicity. Furthermore, certain drugs like dolutegravir or cimetidine can inhibit MATE1/2-K, leading to a benign increase in serum creatinine by blocking its tubular secretion without reflecting a true change in glomerular filtration rate (Lepist et al., 2014, PMID: 24569305).

Other names

OCT1OCT2OCT3MATE1MATE2-KSLC22A1SLC22A2SLC22A3SLC47A1SLC47A2Solute carrier family 22 member 1Solute carrier family 22 member 2Solute carrier family 22 member 3Solute carrier family 47 member 1Solute carrier family 47 member 2

Competitive inhibition of transporter-mediated uptake or efflux; substrate-based transport competition.