RESISTANCE MODIFICATION BY PSC-833, A NOVEL NONIMMUNOSUPPRESSIVE CYCLOSPORINE-A

A novel non-immunosuppressive cyclosporin A, PSC-833, has been tested for its ability to circumvent resistance to doxorubicin, vincristine and colchicine in human and murine multidrug resistantant (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.