Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin [corrected]

A novel non-immunosuppressive cyclosporin [corrected], PSC-833, has been tested for its ability to circumvent resistance to doxorubicin, vincristine and colchicine in human and murine multidrug resistant (MDR) cell lines. This compound is shown to be a highly potent resistance modifier, being 7-10-fold more potent than the parent compound, cyclosporin A, whilst approximately equal to cyclosporin A in the growth inhibitory effects of compound alone. Reversal of the P-glycoprotein-associated MDR drug accumulation defect is a major component of resistance reversal for PSC-833, as it is for cyclosporin A.