Research output: Contribution to journal › Article › peer-review
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.
In: Doklady Biochemistry and Biophysics, Vol. 503, No. 1, 01.04.2022, p. 67-70.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity
AU - Bakhtyukov, A. A.
AU - Derkach, K. V.
AU - Fokina, E. A.
AU - Sorokoumov, V. N.
AU - Zakharova, I. O.
AU - Bayunova, L. V.
AU - Shpakov, A. O.
N1 - Bakhtyukov, A.A., Derkach, K.V., Fokina, E.A. et al. Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity. Dokl Biochem Biophys 503, 67–70 (2022). https://doi.org/10.1134/S1607672922020016
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Abstract: 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.
AB - Abstract: 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.
KW - allosteric agonist
KW - hypothyroidism
KW - receptor of thyroid-stimulating hormone
KW - thyroid gland
KW - thyroid hormone
KW - Hypothyroidism/chemically induced
KW - Animals
KW - Receptors, Thyrotropin
KW - Receptors, G-Protein-Coupled
KW - Thyroxine
KW - Rats
KW - Thyrotropin/pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85130000648&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/8d453d69-6a44-31a1-9ca6-6974ce3dfcd5/
U2 - 10.1134/S1607672922020016
DO - 10.1134/S1607672922020016
M3 - Article
C2 - 35538280
AN - SCOPUS:85130000648
VL - 503
SP - 67
EP - 70
JO - Doklady Biochemistry and Biophysics
JF - Doklady Biochemistry and Biophysics
SN - 1607-6729
IS - 1
ER -
ID: 100025485