Jachez B, Boesch D, Grassberger M A, Loor F
Preclinical Research, Sandoz Pharma Ltd, Basel, Switzerland.
Anticancer Drugs. 1993 Apr;4(2):223-9. doi: 10.1097/00001813-199304000-00015.
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.
FK-506是一种针对肿瘤细胞的耐药调节因子（RMA），其多药耐药性（MDR）涉及P-糖蛋白（Pgp）介导的抗癌药物外排。FK-506的相关物和衍生物家族包括一系列具有不同化学增敏强度的类似物，从无可检测的RMA活性到MDR表型的完全逆转。同样，FK-506类似物也表现出一系列免疫抑制活性，包括无活性的类似物。将FK-506与11种FK-506类似物进行RMA活性比较，这些类似物在抑制双向混合淋巴细胞反应方面的活性至少比FK-506低20倍，它们展现出了整个范围的RMA活性。FK-506的一种这样的强RMA衍生物（SDZ 280-629）进一步被证明能够完全恢复高度耐药的MDR P388肿瘤细胞对柔红霉素的保留。
