Zosuquidar (LY335979) is a widely used experimental P-glycoprotein (P-gp) inhibitor, which is commended as very potent but also as very specific for P-gp. In this in vitro and in silico study, we demonstrated for the first time that zosuquidar also inhibits organic cation transporters (OCT) 1-3, albeit less potently than P-gp. This still has to be kept in mind when zosuquidar is used to inhibit cellular efflux of P-gp substrates that are concurrently transported into the cells by OCTs. To avoid interference in these assays, zosuquidar concentrations should be kept below 1 µM.

Department of Pharmacology and Toxicology Faculty of Pharmacy Charles University Prague Heyrovskeho 1203 50005 Hradec Kralove Czech Republic

Internal Medicine 9 Department of Clinical Pharmacology and Pharmacoepidemiology Heidelberg University Medical Faculty Heidelberg Heidelberg University Hospital Im Neuenheimer Feld 410 69120 Heidelberg Germany

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