phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»10.37489/2587-7836-2024-4-3-16KGXWCFphkinetica-433Research ArticleОБЗОРЫREVIEWSДимерный дипептидный миметик 4-й петли BDNF, потенциальный антидепрессант с новым механизмом действияDimeric dipeptide mimetics of BDNF loop 4 are potential antidepressants with novel mechanisms of actionhttps://orcid.org/0000-0002-5185-4474ГудашеваТ. А.GudashevaT. A.

Гудашева Татьяна Александровна – д. б. н., профессор, член-корреспондент РАН, руководитель отдела химии лекарственных средств

Москва

Tatiana A. Gudasheva – PhD, Dr. Sci. (Biology), Professor, RAS corresponding member, Head of medicinal chemistry department

Moscow

gudasheva@academpharm.ruhttps://orcid.org/0000-0003-3278-8915ПоварнинаП. Ю.PovarninaP. Yu.

Поварнина Полина Юрьевна – к. б. н., в. н. с. лаборатории пептидных биорегуляторов отдела химии лекарственных средств

Москва

Polina Yu. Povarnina – PhD, Cand. Sci. (Biol.), Leading Research Scientist of the Laboratory of Peptide Bioregulators of the Medicinal Chemistry Department

Moscow

https://orcid.org/0000-0001-9750-4157ТарасюкА. В.TarasyukA. V.

Тарасюк Алексей Валерьевич – к. х. н., с. н. с. лаборатории пептидных биорегуляторов отдела химии лекарственных средств

Москва

Alexey V. Tarasyuk – PhD, Cand. Sci. (Chemical), Senior Research Scientist of Laboratory of Peptide Bioregulators of Medicinal Chemistry Department

Moscow

https://orcid.org/0000-0003-2710-7134ЖердевВ. П.ZherdevV. P.

Жердев Владимир Павлович – д. м. н., профессор, заведующий лабораторией фармакокинетики

Москва

Vladimir P. Zherdev – PhD, Dr. Sci. (Med.), professor, Head of laboratory pharmacokinetics

Moscow

https://orcid.org/0000-0003-0912-7684ДурневА. Д.DurnevA. D.

Дурнев Андрей Дмитриевич – д. м. н., профессор, член-корр. РАН, зав. отделом лекарственной токсикологии 

Москва

Andrei D. Durnev – PhD, Dr. Sci. (Med.), professor, corresponding member RAS, Head of the department of drug toxicology

Moscow

ФГБНУ «ФИЦ оригинальных и перспективных биомедицинских и фармацевтических технологий»РоссияFederal research center for innovator and emerging biomedical and pharmaceutical technologiesRussian Federation20242401202504316Copyright © Гудашева Т.А., Поварнина П.Ю., Тарасюк А.В., Жердев В.П., Дурнев А.Д., 20252025Гудашева Т.А., Поварнина П.Ю., Тарасюк А.В., Жердев В.П., Дурнев А.Д.Gudasheva T.A., Povarnina P.Y., Tarasyuk A.V., Zherdev V.P., Durnev A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/433

Представлен обзор собственных работ, посвящённых конструированию, синтезу и фармакологическому изучению оригинального димерного дипептидного миметика 4-й петли мозгового нейротрофического фактора гексаметилендиамида бис-(N-моносукцинил-L-серил-L-лизина (ГСБ-106). Это соединение было сконструировано с использованием авторской технологии создания низкомолекулярных миметиков нейротрофинов и проявило выраженную антидепрессантоподобную активность при системном введении, включая пероральное. Приводятся данные о фармакологических свойствах ГСБ-106 in vitro и in vivo, его механизме действия, о создании и изучении эффектов таблетированной лекарственной формы дипептида, о результатах токсикологических и фармакокинетических исследований.

This review covers original research focused on the design, synthesis, and pharmacological evaluation of an innovative dimeric dipeptide mimetic of brain-derived neurotrophic factor (BDNF) loop 4 bis-(N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide (GSB-106). Developed using a proprietary approach for creating low-molecular-weight neurotrophin mimetics, GSB-106 displayed marked antidepressant-like activity following systemic and oral administration. The article details its pharmacological properties in vitro and in vivo, mechanism of action, development of a tablet form of the dipeptide, and findings from toxicological and pharmacokinetic studies.

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