vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)vedomostiregmed-140Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESМолекулярный поиск перспективных молекул-кандидатов в селективные антагонисты ионного канала TRPA1Molecular screening for potential selective antagonists of TRPA1 ion channelБесхмельницынаЕ. А.BeskhmelnitsynaE. A.noemail@neicon.ruКравченкоД. В.KravchenkoD. V.noemail@neicon.ruПокровскийМ. В.PokrovskyM. V.noemail@neicon.ruКорокинМ. В.KorokinM. V.noemail@neicon.ruПересыпкинаА. А.PeresypkinaA. A.noemail@neicon.ruВаравинЕ. И.VaravinE. I.noemail@neicon.ruКостинаД. А.KostinaD. A.noemail@neicon.ruБелгородский государственный национальный исследовательский университетРоссияBelgorod National Research UniversityRussian FederationИсследовательский институт химического разнообразияРоссияChemical Diversity Research InstituteRussian Federation20171302201873186189Copyright © Бесхмельницына Е.А., Кравченко Д.В., Покровский М.В., Корокин М.В., Пересыпкина А.А., Варавин Е.И., Костина Д.А., 20182018Бесхмельницына Е.А., Кравченко Д.В., Покровский М.В., Корокин М.В., Пересыпкина А.А., Варавин Е.И., Костина Д.А.Beskhmelnitsyna E.A., Kravchenko D.V., Pokrovsky M.V., Korokin M.V., Peresypkina A.A., Varavin E.I., Kostina D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/140

Проведен анализ ряда молекул-кандидатов в селективные антагонисты ионного канала TRPA1 с помощью методов молекулярного моделирования в высокопроизводительном скрининге. Определены их механизмы действия и специфическая активность на клетках с суперэкспрессией ионного канала TRPA1. Подтверждена антагонистическая активность изученных субстанций в отношении ионного канала TRPA1 в результате молекулярного скрининга биологически активных молекул в сравнении с контрольным антагонистом. Установлено, что наибольшая активность проявлена веществом под шифром ZC02-0012, которое является основным кандидатом и может быть рекомендовано для проведения дальнейших исследований безопасности и селективности в тестах in vitro с последующим рядом экспериментов in vivo для определения его активности и безопасности применительно к живым системам.

The article discusses the results of analysis a number of candidate molecules for TRPA1 ion channel selective antagonists using molecular modeling methods of high throughput screening. The study determined their mechanisms of action and specific activity in cells with overexpression of TRPA1 ion channel. It demonstrated antagonistic activity of test substances in relation to TRPA1 ion channel based on the results of molecular screening of biologically active molecules and their comparison with the reference antagonist. The highest activity was demonstrated by the substance with the ZC02-0012 code which was regarded as the main candidate that could be recommended for use in further safety and selectivity studies using in vitro tests and subsequent in vivo experiments aimed at determining its activity and safety in relation to living systems.

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The authors declare that there are no conflicts of interest present.