| In vitro | Biricodar exhibits activity against both P-glycoprotein (Pgp) and MRP-1, enhancing drug uptake and retention while reversing drug resistance mediated by wild-type BCRP (BCRPR482). In Pgp-expressing 8226/Dox6 cells, biricodar increases the uptake of mitoxantrone and daunorubicin by 55% and 100%, respectively. It enhances their retention by 100% and 60%, respectively, and boosts their cytotoxicity by 3.1- and 6.9-fold, respectively. Furthermore, biricodar has similar effects on HL60/Adr cells (MRP-1) and 8226/MR20 cells (BCRP(R482)), but it has little impact on MCF7 AdVP3000 cells (BCRP(R482T))[1]. VX-710, a non-macrocyclic pipecolinate derivative binding to the FK506 receptor protein, has been shown to restore sensitivity in various multidrug-resistant cells, including myeloma, melanoma, carcinoma, and leukemia[2]. Additionally, biricodar effectively inhibits the photoaffinity labeling of P-glycoprotein by [3H]azidopine or [125I]iodoaryl azido-prazosin, with EC50 values of 0.75 and 0.55 μM[3]. |
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