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Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity

To normalize the thyroid status in hypothyroidism caused by resistance to thyroid-stimulating hormone (TSH), low-molecular-weight allosteric agonists of TSH receptor can be used. A new compound ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]-pyrimidine-4-yl)phenyl)-1H-1,2,...

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Autores principales: Bakhtyukov, A. A., Derkach, K. V., Fokina, E. A., Sorokoumov, V. N., Zakharova, I. O., Bayunova, L. V., Shpakov, A. O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pleiades Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090882/
https://www.ncbi.nlm.nih.gov/pubmed/35538280
http://dx.doi.org/10.1134/S1607672922020016
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author Bakhtyukov, A. A.
Derkach, K. V.
Fokina, E. A.
Sorokoumov, V. N.
Zakharova, I. O.
Bayunova, L. V.
Shpakov, A. O.
author_facet Bakhtyukov, A. A.
Derkach, K. V.
Fokina, E. A.
Sorokoumov, V. N.
Zakharova, I. O.
Bayunova, L. V.
Shpakov, A. O.
author_sort Bakhtyukov, A. A.
collection PubMed
description To normalize the thyroid status in hypothyroidism caused by resistance to thyroid-stimulating hormone (TSH), low-molecular-weight allosteric agonists of TSH receptor can be used. A new compound ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]-pyrimidine-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), which stimulated the production of thyroxine when administered to rats (25 mg/kg, i.p.) and also increased the expression of thyroidogenic genes in the cultured FRTL-5 thyrocytes (30 μM) and the rat thyroid gland. The in vitro and in vivo treatment with TPY3m did not lead to a decrease in the expression of the TSH receptor gene in thyrocytes, restoring it under the conditions of receptor hyperactivation by the hormone. This determines the retaining and, in some cases, potentiation of the thyroidogenic effects of TSH (FRTL-5) or thyroliberin (rats) when they are coadministered with TPY3m. TPY3m is a prototype drug for correcting thyroid system functions in subclinical hypothyroidism.
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spelling pubmed-90908822022-05-12 Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity Bakhtyukov, A. A. Derkach, K. V. Fokina, E. A. Sorokoumov, V. N. Zakharova, I. O. Bayunova, L. V. Shpakov, A. O. Dokl Biochem Biophys Biochemistry, Biophysics, and Molecular Biology To normalize the thyroid status in hypothyroidism caused by resistance to thyroid-stimulating hormone (TSH), low-molecular-weight allosteric agonists of TSH receptor can be used. A new compound ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]-pyrimidine-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), which stimulated the production of thyroxine when administered to rats (25 mg/kg, i.p.) and also increased the expression of thyroidogenic genes in the cultured FRTL-5 thyrocytes (30 μM) and the rat thyroid gland. The in vitro and in vivo treatment with TPY3m did not lead to a decrease in the expression of the TSH receptor gene in thyrocytes, restoring it under the conditions of receptor hyperactivation by the hormone. This determines the retaining and, in some cases, potentiation of the thyroidogenic effects of TSH (FRTL-5) or thyroliberin (rats) when they are coadministered with TPY3m. TPY3m is a prototype drug for correcting thyroid system functions in subclinical hypothyroidism. Pleiades Publishing 2022-05-10 2022 /pmc/articles/PMC9090882/ /pubmed/35538280 http://dx.doi.org/10.1134/S1607672922020016 Text en © The Author(s) 2022, ISSN 1607-6729, Doklady Biochemistry and Biophysics, 2022, Vol. 503, pp. 67–70. © The Author(s), 2022. This article is an open access publication.Russian Text © The Author(s), 2022, published in Doklady Rossiiskoi Akademii Nauk. Nauki o Zhizni, 2022, Vol. 503, pp. 161–165. https://creativecommons.org/licenses/by/4.0/Open Access.This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biochemistry, Biophysics, and Molecular Biology
Bakhtyukov, A. A.
Derkach, K. V.
Fokina, E. A.
Sorokoumov, V. N.
Zakharova, I. O.
Bayunova, L. V.
Shpakov, A. O.
Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity
title Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity
title_full Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity
title_fullStr Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity
title_full_unstemmed Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity
title_short Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity
title_sort development of low-molecular-weight allosteric agonist of thyroid-stimulating hormone receptor with thyroidogenic activity
topic Biochemistry, Biophysics, and Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090882/
https://www.ncbi.nlm.nih.gov/pubmed/35538280
http://dx.doi.org/10.1134/S1607672922020016
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