pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2021-9-4-252-265pmedpharm-881Research ArticleОБЗОРЫ, ЛЕКЦИИREVIEWS, LECTURESПРОТИВООПУХОЛЕВЫЕ ПРЕПАРАТЫ НА ОСНОВЕ ПРОИЗВОДНЫХ ИНДОЛОКАРБАЗОЛАANTITUMOR DRUGS BASED ON INDOLOCARBAZOL DERIVATIVEShttps://orcid.org/0000-0001-9388-1019КолпаксидиА. П.KolpaksidiI. P.

аспирант кафедры фармацевтической технологии Института Фармации ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России (Сеченовский Университет); лаборант-исследователь лаборатории разработки лекарственных форм НИИ экспериментальной диагностики и терапии опухолей ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России

post-graduate student of the Department of Pharmaceutical Technology of the Institute of Pharmacy I.M. Sechenov First Moscow State Medical University (Sechenov University); laboratory assistant-researcher Laboratory for the Development of Dosage Forms Research Institute for Experimental Diagnostics and Therapy of Tumors N.N. Blokhin National Medical Research Center of Oncology

aleksandrkolpaksidi@gmail.comhttps://orcid.org/0000-0001-6740-5692ДмитриеваМ. В.DmitrievaM. V.

кандидат фармацевтических наук, старший научный сотрудник лаборатории разработки лекарственных форм НИИ экспериментальной диагностики и терапии опухолей 

Candidate of Sciences (Pharmacy), Senior Researcher Laboratory for the Development of Dosage Forms Research Institute for Experimental Diagnostics and Therapy of Tumors

dmitrieva.m@ronc.ruhttps://orcid.org/0000-0002-3347-9674ЯрошИ. В.YaroshI. V.

ординатор кафедры фармацевтической технологии Института Фармации 

resident of the Department of Pharmaceutical Technology of the Institute of Pharmacy 

ilya96yarosh@gmail.comhttps://orcid.org/0000-0003-4382-7377КраснюкИ. И.KrasnyukI. I.

доктор фармацевтических наук, профессор, заведующий кафедрой фармацевтической технологии Института Фармации

Doctor of Sciences (Pharmacy), Professor, head of the Department of Pharmaceutical Technology of the Institute of Pharmacy 

krasnyuki@mail.ru1. Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский университет) 119991, Россия, г. Москва, ул. Трубецкая, д. 8, стр. 2 2. Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации 115478, Россия, г. Москва, Каширское ш., д. 24Россия1. I.M. Sechenov First Moscow State Medical University (Sechenov University) Bldg. 2, 8, Trubetskaya St., Moscow, Russia, 119991 2. N.N. Blokhin National Medical Research Center of Oncology 24, Kashirskoe sh., Moscow, Russia, 115478Russian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Министерства здравоохранения Российской Федерации 115478, Россия, г. Москва, Каширское ш., д. 24РоссияN.N. Blokhin National Medical Research Center of Oncology 24, Kashirskoe sh., Moscow, Russia, 115478Russian FederationФедеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский университет) 119991, Россия, г. Москва, ул. Трубецкая, д. 8, стр. 2РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University) Bldg. 2, 8, Trubetskaya St., Moscow, Russia, 119991Russian Federation20210709202194252265Copyright © Колпаксиди А.П., Дмитриева М.В., Ярош И.В., Краснюк И.И., 20212021Колпаксиди А.П., Дмитриева М.В., Ярош И.В., Краснюк И.И.Kolpaksidi I.P., Dmitrieva M.V., Yarosh I.V., Krasnyuk I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/881Цель

Цель. Обобщение литературных данных о производных индолокарбазола, обладающих противоопухолевой активностью.

Материалы и методы

Материалы и методы. Объектом изучения являлись препараты на основе производных индолокарбазола с противоопухолевой активностью. Для поиска материалов по исследуемой проблеме использовали следующие поисково-информационные и библиотечные базы данных: ebibrary, PubMed, CyberLeninka, ResearchGate, а также Государственный реестр лекарственных средств, реестры клинических исследований clinline.ru и clinicaltrials.gov. Поиск проводился по следующим словам/словосочетаниям: индолокарбазолы (indolocarbazoles), производные индолокарбазолов (indolocarbazole derivatives), стауроспорин (staurosporine), ребеккамицин (rebeccamycin), производные стауроспорина (staurosporine derivatives), производные ребеккамицина (rebeccamycin derivatives). Поиск проводился с 11 января по 1 марта 2021 года; учитывались соединения с биологической активностью, проходящие или прошедшие доклинические и клинические испытания. Учитывались все материалы с 1977 года по 1 января 2021.

Результаты

Результаты. Полученные материалы свидетельствуют о том, что производные индолокарбазола являются перспективными соединениями для создания противоопухолевых лекарственных препаратов благодаря их свойствам и особенностям механизма действия. Данные препараты обладают избирательностью действия, что обусловлено направленным взаимодействием с конкретными молекулярными мишенями: киназы (особенно протеинкиназа C и её изоферменты), ДНК и ДНК-топоизомеразы. К настоящему времени синтезировано и исследовано множество соединений из класса индолокарбазолов, показавших высокую противоопухолевую активность при терапии системных и солидных опухолей. Однако несмотря на это, только один лекарственный препарат на основе производного стауроспорина, зарегистрированный под ТН Rydapt® (в США и странах Евросоюза) и Митикайд® (в Российской Федерации), разрешен для применения в клинике.

Заключение

Заключение. Таким образом проведено обобщение основных данных из научных публикаций, посвященным перспективным противоопухолевым препаратам на основе соединений из класса индолокарбазолов. В частности, приведены сведения об их молекулярном строении, происхождении, классификации, основных представителях класса, находящихся на различных стадиях исследований и разрешенных к применению в клинической практике.

The aim of the work is to generalize the literature data on indolocarbazole derivatives with an antitumor activity.

Materials and methods

Materials and methods. The objects of the study were the preparations based on indolocarbazole derivatives with the antitumor activity. To search for materials on the problem under study, the following search and information as well as library databases were used: ebibrary, PubMed, CyberLeninka, ResearchGate, the State Register of Medicines, clinical trials registries clinline.ru and clinicaltrials.gov. The search for the following words / phrases was performed: indolocarbazoles, indolocarbazole derivatives, staurosporine, rebeccamycin, staurosporine derivatives. The search was conducted from January 11 until March 1, 2021. The compounds with a biological activity which were undergoing or had undergone preclinical and clinical trials, were taken into account. All the materials from 1977 to January 1, 2021, were taken into account.

Results

Results. The materials obtained indicate that indolocarbazole derivatives are promising compounds for the creation of anticancer medicinal preparations due to their properties and peculiarities of the action mechanism. These drugs have a selective action due to the targeted interaction with specific molecular targets: kinases (especially protein kinase C and its isozymes), DNA and DNA topoisomerase. To date, many compounds from the class of indolocarbazoles have been synthesized and investigated. They have shown a high antitumor activity in the treatment of systemic and solid tumors. However, despite this, only one MP based on a staurosporine derivative, registered by the TN of Rydapt® (in the USA and EU countries) and Miticaid® (in the Russian Federation), is approved for use in the clinical practice.

Conclusion

Conclusion. Thus, the basic data from scientific publications on promising anticancer medicinal preparations based on compounds from the class of indolocarbazoles, have been summarized. The information is provided, in particular, on their molecular structure, the origin, classification, the main representatives of the class, which are at various stages of the research and are approved for use in the clinic.

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