22,抑制多药耐药性protein-mediated流出的蒽环霉素和calceinacetoxymethyl酯pak - 104 p。

文章的细节

引用

复制到剪贴板

Marbeuf-Gueye C, Salerno M, Quidu P, Garnier-Suillerot

22,抑制多药耐药性protein-mediated流出的蒽环霉素和calceinacetoxymethyl酯pak - 104 p。

欧元J杂志。2000年3月17日,391 (3):207 - 16。

PubMed ID

10729360 (在PubMed

]

文摘

哺乳动物细胞的多药耐药性表型往往是与过度的22或多重Resistance-Associated蛋白(MRP (1))。蛋白质都是能量依赖性药物流出泵有效减少细胞内积累,因此许多自然细胞毒素的细胞毒性。超表达这些转运蛋白的肿瘤细胞被认为是一个重要因素内在和获得性耐药的抗癌药物。因此大量的兴趣主要集中在识别化学药剂,可以抵销这些蛋白质药物运输或者可以抑制肿瘤细胞的增殖,尽管这些转运蛋白的表达。P-glycoprotein-mediated多药耐药性的逆转是多种化合物,但令人惊讶的是,一些代理扭转MRP(1)介导多药耐药性。然而,它最近表明,2 - [4 - (diphenylmethyl) 1-piperazinyl] ethyl-5——(trans-4 6-dimethyl-1 3, 2-dioxaphosphorinan-2-yl) 2, 6-dimethyl-4 -氧化(3-nitrophenyl) 3-pyridinecarboxylate P (pak - 104 P)能够抑制22和MRP(1)介导流出的几个化合物。转运蛋白之间的相互作用的理解和多药耐药性逆转剂是重要的设计更有效的多药耐药性调节器。我们现在检查pak - 104 p的影响在pgp和MRP1-mediated流出三个蒽环霉素、柔毛霉素,pirarubicin, hydroxydoxorubicin和钙黄绿素acetoxymethyl酯和钙黄绿素。我们的数据表明,pak - 104 p非竞争性抑制P-glycoprotein-mediated流出的蒽环霉素衍生品和钙黄绿素acetoxymethyl酯的抑制常数K (I) = 0。25 + / - -0.05 microM。 PAK-104P also non-competitively inhibits the MRP(1)-mediated efflux of daunorubicin, pirarubicin, hydroxyrubicin, calcein acetoxymethyl ester and calcein. However, surprisingly, in this case the K(I) values obtained were very different ranging from 0.06 for hydroxyrubicin to 10 microM for calcein. These data strongly suggested the existence of two different mechanisms for the inhibition by PAK-104P of the MRP(1)-mediated efflux of molecules: a first mechanism, involving a low-affinity site for PAK-104P, and which would concern molecules such as calcein, cysteinyl leukotriene LCT(4) etc. whose efflux do not depend on glutathione. A second mechanism involving a high-affinity site for PAK-104P and which would concern molecules such as anthracyclines, calcein acetoxymethyl ester whose efflux depends on the presence of glutathione.

DrugBank数据引用了这篇文章

药物转运蛋白

药物	转运体	类	生物	药理作用	行动
道诺霉素	耐多药resistance-associated蛋白1	蛋白质	人类	未知的	底物 抑制剂	细节