Regulation of 11β-hydroxysteroid dehydrogenase isoforms – novel drug targets for osteoporosis therapy

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.11.807

Abstract

Introduction: Osteoporosis is an significant medical and social public health problem in an aging or elderly society, the issue of pharmacological correction of which remains unresolved to this day.

Materials and Methods: The rationale for this idea stems from our previous findings on the role of 11B-HSD type 2 in bone remodeling and osteoreparation, combined with a content analysis and literature review of scientific publications from PubMed, Scopus, Cyberleninka, Google Scholar, and ResearchGate.

Results and Discussion: Current understanding of the molecular mechanisms of bone homeostasis allows for a significant shift and expansion in the paradigms for treating and preventing osteoporosis. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key metabolic enzyme that catalyzes the intracellular conversion of inactive glucocorticoids into physiologically active ones. Research conducted over the past decade has shown that abnormal 11β-HSD1 activity contributes to the pathogenesis of obesity, type 2 diabetes, metabolic syndrome, and osteoporosis. The scientific challenge of regulating the activity of 11β-hydroxysteroid dehydrogenase (11β-HSD) isoforms and restoring homeostasis in the 11β-HSD1/11β-HSD2 enzymatic system is proposed to be addressed through the design and application of novel azole-based heterocyclic compounds as 11β-HSD1 inhibitors.

Conclusion: The development of azole-based heterocyclic 11β-HSD1 inhibitors is expected to yield promising drug candidates for pharmacologically correcting impaired bone remodeling and repair.

Graphical Abstract

Keywords:

osteoporosis, 11β-hydroxysteroid dehydrogenase, regulation, 11β-HSD inhibitors, drug targets

References

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Author Contribution

Ivan S. Koklin, Belgorod State National Research University

Cand. Sci. (Medicine), Researcher at the Research Institute of Pharmacology of Living Systems, Belgorod State National Research University, Belgorod, Russia; e-mail:  ikoklin@mail.ru; ORCID ID:  https://orcid.org/0000-0002-1560-4195. Developing a research design, processing the results obtained, and writing the

Petr R. Lebedev, Belgorod State National Research University

MD, Junior Researcher at the Laboratory of Genetic Technologies and Gene Editing for Biomedicine and Veterinary Science, Belgorod State National Research University, Russia; e-mail: artkelt98@yandex.ru; ORCID ID: https://orcid.org/0000-0001-9102-3360. Review of the  published data.

Alim A. Kochkarov, Belgorod State National Research University

MD, Researcher at the Research Institute of Pharmacology of Living Systems, Belgorod State National Research University, Belgorod, Russia; e-mail: kochkarova@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0003-4972-7262. Review of the published data.

Oleg S. Gudyrev, Belgorod State National Research University

Cand. Sci. (Medicine), Associate Professor at the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: gudyrev@mail.ru; ORCID ID: https://orcid.org/0000-0003-0097-000X. Developing a research design, processing the results obtained, and writing the article.

Vladimir V. Gureev, Belgorod State National Research University

Doctor Habil. of Medical Sciences, Associate Professor, Professor of the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: produmen@mail.ru; ORCID ID: https://orcid.org/0000-0003-1433-1225. Developing a research design, processing the results obtained, and writing the article.

Aleksandr A. Dolzhikov, Belgorod State National Research University

Doctor Habil. of Sciences (Medicine), Professor of the Department of Human Anatomy and Histology, Belgorod State National Research University, Belgorod, Russia; e-mail: dolzhikov@bsu.edu.ru; ORCID ID: https://orcid.org/0000-0001-7425-8416. Developing a research design, processing the results obtained, and writing the article.

Eduard I. Taran, Belgorod State National Research University

MD, Researcher at the Research Institute of Pharmacology of Living Systems, Belgorod State National Research University, Belgorod, Russia; e-mail: mdtaraneduard@gmail.com; ORCID ID: https://orcid.org/0000-0001-7880-6686. Study of bone density and formation of experimental cohorts.

Mikhail V. Korokin, Belgorod State National Research University

Doct. Habil. Sci. (Medicine), Professor at the Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: mkorokin@mail.ru; ORCID ID: https://orcid.org/0000-0001-5402-0697. Developing a research design, processing the results obtained, and writing the article.

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Published

30-09-2025

How to Cite

Koklin IS, Lebedev PR, Kochkarov AA, Gudyrev OS, Gureev VV, Dolzhikov AA, Taran EI, Korokin MV (2025) Regulation of 11β-hydroxysteroid dehydrogenase isoforms – novel drug targets for osteoporosis therapy. Research Results in Pharmacology 11(3): 109–114. https://doi.org/10.18413/rrpharmacology.11.807

Issue

Vol. 11 No. 3 (2025)

Section

Short Communication

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Copyright (c) 2025 Koklin IS, Lebedev PR, Kochkarov AA, Gudyrev OS, Gureev VV, Dolzhikov AA, Taran EI, Korokin MV

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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