medjournalМедицинский журналMedical Journal1818-426XБелорусский государственный медицинский университет10.51922/1818-426X.2023.2.62medjournal-232Research ArticleОРИГИНАЛЬНЫЕ НАУЧНЫЕ ПУБЛИКАЦИИORIGINAL SCIENTIFIC PUBLICATIONSИсследование In Silico аффинности ривароксабана к глюкокиназеIn Silico study of rivaroxaban affinity to glucokinaseЛахвичФ. Ф.LakhvichT.РинейскаяО. Н.RyneiskayaV.УО «Белорусский государственный медицинский университет»Belarus202320062025026266Copyright © Лахвич Ф.Ф., Ринейская О.Н., 20252025Лахвич Ф.Ф., Ринейская О.Н.Lakhvich T., Ryneiskaya V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://medjournal.ejournal.by/jour/article/view/232

Сахарный диабет 2-го типа является актуальной проблемой современного здравоохранения. Сравнение структуры Ривароксабана со строением ряда экспериментальных лекарственных средств, активаторов глюкокиназы, показало перспективность его исследования для разработки лекарственных средств для лечения диабета 2 типа. В исследованиях in silico изучено взаимодействие Ривароксабана с глюкокиназой, которая участвует в фосфорилировании глюкозы клеток печени и поджелудочной железы. При помощи методов молекулярного докинга получены комплексы Ривароксабана с протеином в аллостерическом центре, который отвечает за действие активаторов глюкокиназы: минимальная энергия связывания – 9,41 ккал/моль. Полученные результаты открывают перспективу разработки новых эффективных противодиабетических лекарственных средств и изучения сопутствующего действия антикоагулянта Ривароксабана.

Type 2 diabetes mellitus is an urgent problem of health care. Comparison of the structure of the Rivaroxaban with the structure of a number of experimental drugs, which are Glucokinase activators, revealed the perspectives of its evaluation in the drug design for the treatment of type 2 diabetes. In in silico experiments, the interaction of Rivaroxaban with glucokinase, which is involved in glucose phosphorylation in liver and pancreas cells, has been studied. Using molecular docking methods, complexes of Rivaroxaban with a protein in the allosteric center responsible for the action of glucokinase activators, were generated: the minimum binding energy was found 9.41 kcal/mol. The results obtained in the experiment in silico open the perspectives of design and development of the new effective antidiabetic drugs as well as investigation of the concomitant action of the anticoagulant Rivaroxaban.

активаторы глюкокиназыаллостерический центрмолекулярный докингРивароксабансахарный диабетallosteric centerdiabetes mellitusglucokinase activatorsmolecular dockingRivaroxabanReferencesInzucchi, S. E. Current Therapies for the Medical Management of Diabetes. Obstet Gynecol. / S. E. Inzucchi, S. K. Majumdar // Obsterics & Gynecol. – 2016. – Vol. 127(4). – P. 780–794. – doi: 10.1097/AOG.0000000000001332.Inzucchi, S. E. Current Therapies for the Medical Management of Diabetes. Obstet Gynecol / S. E. Inzucchi, S. K. Majumdar // Obsterics & Gynecol. – 2016. – Vol. 127(4). – P. 780– 794. – doi: 10.1097/AOG.0000000000001332.Lenzen, S. A. fresh view of glycolysis and glucokinase regulation: history and current status // J. Biol. Chem. – 2014. – Vol. 289. – P. 12189–94.Lenzen, S. A. fresh view of glycolysis and glucokinase regulation: history and current status // J. Biol. Chem. – 2014. – Vol. 289. – P. 12189–94.Del Guerra, S. Functional and molecular defects of pancreatic islets in human type 2 diabetes / S. Del Guerra, R. Lupi, L. Marselli [et al.] // Diabetes. – 2005. – Vol. 54. – P. 727–35.Del Guerra, S. Functional and molecular defects of pancreatic islets in human type 2 diabetes / S. Del Guerra, R. Lupi, L. Marselli [et al.] // Diabetes. – 2005. – Vol. 54. – P 727–35.Yixin, Ren. Glucokinase as an emerging anti­diabetes target and recent progress in the development of its agonists / Yixin Ren [et al.] // Journal of Enzyme Inhibition and Medicinal Chemistry. – 2022. – Vol. 37(1). – P. 606–615.Yixin, Ren. Glucokinase as an emerging anti-diabetes target and recent progress in the development of its agonists / Yixin Ren [et al.] // Journal of Enzyme Inhibition and Medicinal Chemistry. – 2022. – Vol. 37(1). – P. 606–615.Tsumura, Y. TMG123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models / Y. Tsumura [et al.] // PLoS ONE. – 2017. – Vol. 12(2). – P. e0172252.Tsumura, Y. TMG123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models / Y. Tsumura [et al.] // PLoS ONE. – 2017. – Vol. 12(2). – Р. e0172252.Lakhvich, T. T. In silico SAR studies of oxazolidinones as potential anti­tuberculosis drugs. Advances in medicine and medical sciences: collection of Belarusian state medical university / T. T. Lakhvich, M. I. Borava, V. M. Ryneiskaya. – 2022. – Vol. 12(2). – P. 200–205.Lakhvich, T. T. In silico SAR studies of oxazolidinones as potential anti-tuberculosis drugs / Lakhvich T. T. Lakhvich, M. I. Borava, V. M. Ryneiskaya // Advances in medicine and medical sciences: collection of Belarusian state medical university. – 2022. – Vol. 12(2). – Р. 200–205.Ronald, J. Hinklin. Discovery of 2­Pyridylureas as Glucokinase Activators. Journal of Medicinal Chemistry / Ronald J. Hinklin [et al.] // Journal of Medicinal Chemistry. – 2014. – Vol. 57(19). – P. 8180–8186.Ronald, J. Hinklin. Discovery of 2-Pyridylureas as Glucokinase Activators / Ronald J. Hinklin [et al.] // Journal of Medicinal Chemistry. – 2014. – Vol. 57(19). – P. 8180–8186.Kamata, K. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase / K. Kamata, M. Mitsuya, T. Nishimura, J. Eiki // Structure. – 2004. – Vol. 12(3). – P. 429–38.Kamata, K. Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase / K. Kamata, M. Mitsuya, T. Nishimura, J. Eiki // Structure. – 2004. – Vol. 12(3). – P. 429–38.Tsumura, Y. Disruptions in hepatic glucose metabolism are involved in the diminished efficacy after chronic treatment with glucokinase activator / Y. Tsumura [et al.] // PLoS ONE. – 2022. – Vol. 17(3). – Р. e0265761.Tsumura, Y. Disruptions in hepatic glucose metabolism are involved in the diminished efficacy after chronic treatment with glucokinase activator / Y. Tsumura [et al.] // PLoS ONE. – 2022. – Vol. 17(3). – Р. e0265761.

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