Multidrug and toxin extrusion protein 1 and Organic cation transporter 2 (MATE1/OCT2)

MATE1 (Multidrug and toxin extrusion protein 1) and OCT2 (Organic cation transporter 2) are critical membrane transporters that work in a coordinated manner to facilitate the renal secretion of organic cations [1.1.1, 1.3.1]. OCT2 is localized to the basolateral membrane of renal proximal tubule cells, where it mediates the uptake of cationic drugs and endogenous compounds from the blood into the cells [1.1.2, 1.4.1]. MATE1 is located on the apical membrane and acts as an H+/organic cation antiporter to extrude these substances into the tubular lumen for excretion in the urine [1.1.2, 1.4.4]. This transporter system is a major determinant of the pharmacokinetics and elimination of numerous clinically significant drugs, most notably the antidiabetic agent metformin [1.1.4, 1.3.1]. Inhibition of MATE1 and/or OCT2 by perpetrator drugs can lead to significant drug-drug interactions, resulting in elevated plasma concentrations of substrate drugs and an increased risk of toxicity [1.1.1, 1.2.1]. For example, inhibition of this pathway can lead to metformin-associated lactic acidosis or increased cisplatin-induced nephrotoxicity [1.3.1, 1.4.3]. Consequently, these transporters are critical targets for regulatory-mandated interaction studies during drug development to ensure patient safety [1.1.2, 1.2.4]. They also play a role in the disposition of endogenous biomarkers like creatinine and N-methylnicotinamide [1.2.2, 1.2.4].

Other names

SLC47A1SLC22A2MATE1OCT2hMATE1hOCT2Solute carrier family 47 member 1Solute carrier family 22 member 2

Inhibition of renal tubular secretion of organic cations via competitive or non-competitive binding to the OCT2 uptake or MATE1 efflux transporters [1.1.2, 1.2.4].