Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin A

Peter R. Twentyman, Norman M. Bleehen
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引用次数: 117

Abstract

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.

新型非免疫抑制性环孢素a PSC-833的耐药修饰
一种新型的非免疫抑制环孢素A PSC-833在人类和小鼠多药耐药(MDR)细胞系中被测试能够规避对阿霉素、长春新碱和秋水仙碱的耐药性。该化合物被证明是一种高效的耐药性调节剂,比母体化合物环孢素a的效力高7 - 10倍,而在单独的生长抑制作用方面,该化合物与环孢素a大致相当。p糖蛋白相关耐多药药物积累缺陷的逆转是PSC-833耐药逆转的主要组成部分,环孢素a也是如此。
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