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The “specific” P-glycoprotein inhibitor zosuquidar (LY335979) also weakly inhibits human organic cation transporters

  • Gzona Bajraktari-Sylejmani,
  • Rajamanikkam Kamaraj,
  • Dirk Theile,
  • Petr Pávek,
  • Johanna Weiss

摘要

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.