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 -