Reversion of the P-glycoprotein-mediated multidrug resistance of cancer cells by FK-506 derivatives.

Abstract

FK-506 is a resistance-modulating agent (RMA) for tumor cells whose multidrug resistance (MDR) involves a P-glycoprotein (Pgp)-mediated anti-cancer drug efflux. The family of FK-506 relatives and derivatives includes analogs which display a whole range of chemosensitizing strengths, from no detectable RMA activity to a complete reversion of the MDR phenotype. Similarly, FK-506 analogs display a whole range of immunosuppressive activities, including inactive ones. FK-506 was compared for RMA activity with 11 FK-506 analogs which were at least 20-fold less active than FK-506 for the inhibition of the bi-directional mixed lymphocyte reaction displayed the whole range of RMA activity. One such strong RMA derivative of FK-506 (SDZ 280-629) was further shown able to restore completely daunomycin retention by highly resistant MDR P388 tumor cells.

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@article{Jachez1993ReversionOT, title={Reversion of the P-glycoprotein-mediated multidrug resistance of cancer cells by FK-506 derivatives.}, author={B. Jachez and Danielle Boesch and Maximilian A. Grassberger and Francis Loor}, journal={Anti-cancer drugs}, year={1993}, volume={4 2}, pages={223-9} }