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Solute carrier family 22 member 11, commonly known as Organic anion transporter 4 (OAT4), is a multispecific transporter primarily expressed in the apical membrane of renal proximal tubule cells and the basal membrane of placental syncytiotrophoblasts [1, 8, 10]. In the kidney, OAT4 functions as an organic anion/dicarboxylate exchanger that facilitates the reabsorption of urate and the secretion of various drugs and toxins [2, 14, 15]. In the placenta, it plays a critical role in the uptake of fetal-derived steroid sulfates, such as dehydroepiandrosterone sulfate (DHEA-S), and protects the fetus by clearing xenobiotics [1, 11, 12]. OAT4 is a significant therapeutic target for the treatment of hyperuricemia and gout, where drugs like lesinurad inhibit its activity to promote urinary urate excretion [2, 6, 15]. Beyond its role in urate homeostasis, OAT4 is a major site for drug-drug interactions because it interacts with a wide range of pharmaceuticals, including diuretics, NSAIDs, and antibiotics [6, 9, 13]. Inhibition or competition at this transporter can lead to altered pharmacokinetics and potential nephrotoxicity of co-administered drugs [2, 13, 15]. Consequently, OAT4 is a key focus in drug development and safety assessments to predict and mitigate adverse clinical outcomes [6, 16].
Inhibition of renal urate reabsorption via organic anion/dicarboxylate exchange
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