ИНГИБИТОРЫ ЦИНК-ЗАВИСИМЫХ ГИСТОНДЕАЦЕТИЛАЗ (HDAC): ТЕРАПЕВТИЧЕСКИЙ ПОТЕНЦИАЛ, СТРУКТУРА ФАРМАКОФОРА И МЕТОДЫ ТЕСТИРОВАНИЯ ДЕАЦИЛАЗНОЙ АКТИВНОСТИ

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Аннотация

В 1976 году среди метаболитов бактерии Streptomyces hygroscopicus был найден противогрибковый гидроксамовый антибиотик трихостатин А (TSA). Потребовалось 14 лет, чтобы выяснить, что TSA ингибирует активность гистондеацетилаз (HDAC) и влияет тем самым на пролиферацию и дифференцировку клеток млекопитающих. К 2015 году была создана единая база данных, содержащая структуры около 1050 синтетических и 400 природных ингибиторов HDAC. В настоящее время пять ингибиторов HDAC разрешены к применению в качестве противоопухолевых средств и еще десятки соединений проходят клинические испытания. Однако внедрение новых препаратов сильно тормозится многонаправленностью их действия и тяжестью побочных эффектов. Для преодоления этих проблем необходимы новые стратегии, включая разработку ингибиторов, нацеленных на определенный класс HDAC. В представленном обзоре обсуждаются не только важнейшие характеристики HDAC и их природных ингибиторов, рассматриваются также современные подходы к дизайну селективных ингибиторов HDAC и методы, применяемые для их тестирования.

Об авторах

А. С. Земская

Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук

Москва, 119991 Россия

С. Н Кочетков

Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук

Москва, 119991 Россия

М. В. Козлов

Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук

Email: kozlovmavi@gmail.com
Москва, 119991 Россия

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