БИОХИМИЯ, 2019, том 84, вып. 2, с. 191–211

УДК 615.012.1

Компьютерный дизайн низкомолекулярных ингибиторов факторов системы свертывания крови

Обзор

© 2019 А.С. Кабанкин 1, Е.И. Синауридзе 1,2, Е.Н. Липец 1,2, Ф.И. Атауллаханов 1,2,3,4*

1 Центр теоретических проблем физико-химической фармакологии РАН, 119991 Москва, Россия; электронная почта: ataullakhanov.fazly@gmail.com

2 Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева, Министерство здравоохранения России, 117198 Москва, Россия

3 Московский государственный университет им. М.В. Ломоносова, физический факультет, 119991 Москва, Россия

4 Московский физико-технический институт, 141701 Долгопрудный Московской области Россия

Поступила в редакцию 05.09.2018
После доработки 19.10.2018
Принята к публикации 19.10.2018

DOI: 10.1134/S0320972519020039

КЛЮЧЕВЫЕ СЛОВА: антикоагулянты, низкомолекулярные ингибиторы, факторы свертывания крови, компьютерный дизайн ингибиторов, молекулярный докинг.

Аннотация

Представлен обзор основных подходов к поиску новых низкомолекулярных ингибиторов факторов свертывания крови IIa, Xa, IXa и XIa, а также результаты этого поиска, проведенного с 2015 по 2018 г. Для каждого из перечисленных факторов за последнее время найдено по несколько ингибиторов с IC50 менее 10 нМ. Некоторые из них находятся на стадии клинических испытаний. Однако ни одно из этих соединений не подходит на роль «идеального» антикоагулянта, поэтому дальнейший поиск таких ингибиторов является актуальной задачей.

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Финансирование

Работа поддержана грантом по программе фундаментальных исследований Президиума РАН «Фундаментальные основы технологии физиологических адаптаций», раздел «Новые ингибиторы тромбина» — грантом РНФ 16-14-00224.

Конфликт интересов

Авторы работы декларируют отсутствие конфликта интересов.

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