Biopolym. Cell. 2017; 33(4):291-301.
Биоорганическая химия
Идентификация хит-соединений – ингибиторов СК2 методами виртуального скрининга.
1, 2Протопопов Н. В., 2Старосила С. А., 2Боровиков А. В., 2Сапелкин В. Н., 3Белоконь Я. В., 2Бджола В. Г., 2Ярмолюк С. М.
  1. Киевский национальный университет имени Тараса Шевченко
    ул. Владимирская, 64, Киев, Украина, 01601
  2. Институт молекулярной биологии и генетики НАН Украины
    ул. Академика Заболотного, 150, Киев, Украина, 03680
  3. Otava
    400 Applewood Crescent, Unit 100, Vaughan, Онтарио, L4K 0C3 Канада

Abstract

Цель. Поиск новых химических соединений со способностью ингибировать протеинкиназу СК2. Методы. Виртуальный скрининг библиотеки низкомолекулярных органических соединений осуществляли при помощи методов молекулярного докинга программным пакетом Autodock 4.2.6 и фармакофорного моделирования – программой «PharmDeveloper». Активность ингибиторов изучали при помощи биохимических тестов in vitro, используя γ-P32 ATФ). Результаты. По результатам виртуального скрининга было отобрано 298 соединений для in vitro исследования. Биохимическое тестирование показало, что 18 соединений показали способность ингибировать протеинкиназу СК2 в диапазоне значений IC50 от 1.4 до 20 μМ. Активные соединения являются производными от 15 химических классов. Выводы. Используя методы молекулярного моделирования и биохимического тестирования было обнаружено ряд ингибиторов протеинкиназиы СК2, со значением LE выше 0.3, которые являются перспективными для последующей оптимизации с целью разработки на их основе лекарственных средств.
Keywords: Протеинкиназа СК2, молекулярный докинг, фармакофорное моделирование, виртуальный скрининг, in vitro тестирование

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