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Molecular-biological problems of drug design and mechanism of drug action

Hydrophilic hexapeptides: a new class of regulators of atp-dependent transport proteins of multiple drug resistance

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Multiple drug resistance (MDR) appears as a result of sharply increased elimination of drugs from a cell into the extracellular space by ATP-dependent transport proteins. At present, no effective inhibitor of transport proteins is available that could be used to overcome MDR. The influence of two hydrophilic hexapeptides, imunofan and biopoetin, on the activity and amount of transport proteins responsible for MDR formation has been investigated using cell lines of human throat cancer (Hep-2), human oral cavity carcinoma (KB8-5), and human prostate cancer (PC-3). The effect of the hexapeptides was evaluated by comparing the Rh 123 expulsion rate and the expression of transport proteins and their genes. It is established that the indicated hydrophilic hexapeptides in very low concentrations (of the order of 10 – 10 M) inhibit the substrate expulsion from a cell into the extracellular space. However, the two hydrophilic hexapeptides modulate MDR by different mechanisms. Imunofan and biopoetin are the first tumor MDR inhibitors showing activity at such low concentrations.

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Authors and Affiliations

  1. Central Research Institute of Epidemiology, ul. Novogireevskaya 3a, Moscow, 111123, Russia

    V. V. Lebedev & S. A. Novikov

  2. Blokhin Oncological Research Center, Russian Academy of Medical Sciences, Kashirskoe shosse 24, Moscow, 115478, Russia

    E. Yu. Rybalkina & T. N. Zabotina

Authors
  1. V. V. Lebedev
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  2. S. A. Novikov
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  3. E. Yu. Rybalkina
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  4. T. N. Zabotina
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Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 11, pp. 3 – 6, November, 2009.

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Lebedev, V.V., Novikov, S.A., Rybalkina, E.Y. et al. Molecular-biological problems of drug design and mechanism of drug action. Pharm Chem J 43, 593–596 (2009). https://doi.org/10.1007/s11094-010-0359-z

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  • DOI: https://doi.org/10.1007/s11094-010-0359-z

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