Multidrug and toxic compound extrusion protein 1 (MATE1)

Multidrug and toxic compound extrusion protein 1 (MATE1), encoded by the SLC47A1 gene, is a critical transmembrane transporter primarily expressed on the apical membranes of renal proximal tubule cells and the canalicular membranes of hepatocytes [1, 2]. It functions as a proton-coupled antiporter, facilitating the excretion of various organic cations and xenobiotics from the blood into the urine and bile [4]. MATE1 plays a pivotal role in the pharmacokinetics of numerous drugs, most notably the first-line antidiabetic agent metformin, where it mediates its renal secretion [5]. Genetic polymorphisms in MATE1 have been associated with altered glycemic response to metformin and variations in the clearance of other cationic drugs [5]. Because many clinically used drugs are potent inhibitors of MATE1, it is a major focus of regulatory guidelines for evaluating drug-drug interactions (DDIs) [3]. Inhibition of MATE1 can lead to elevated plasma levels of co-administered substrates, potentially increasing the risk of toxicity or affecting endogenous metabolite levels, such as creatinine [3, 4]. Sources: [1] UniProt (Q96FL8); [2] NCBI Gene (55244); [3] FDA In Vitro Drug Interaction Guidance; [4] PMID: 16272227; [5] PMID: 21144661.

Other names

Solute carrier family 47 member 1SLC47A1hMATE1

Drugs interact with MATE1 either as substrates for efflux transport or as inhibitors that block the transport of other cationic compounds, thereby altering their systemic clearance.