TY - JOUR

T1 - The Study of Biological Activity of a New Thieno[2,3-D]-Pyrimidine-Based Neutral Antagonist of Thyrotropin Receptor

AU - Derkach, K. V.

AU - Fokina, E. A.

AU - Bakhtyukov, A. A.

AU - Sorokoumov, V. N.

AU - Stepochkina, A. M.

AU - Zakharova, I. O.

AU - Shpakov, A. O.

N1 - Derkach, K.V., Fokina, E.A., Bakhtyukov, A.A. et al. The Study of Biological Activity of a New Thieno[2,3-D]-Pyrimidine-Based Neutral Antagonist of Thyrotropin Receptor. Bull Exp Biol Med 172, 713–717 (2022). https://doi.org/10.1007/s10517-022-05462-x

PY - 2022/4

Y1 - 2022/4

N2 - The development of low-molecular-weight antagonists of thyroid-stimulating hormone (TSH) receptor is a promising trend in the treatment of autoimmune hyperthyroidism. We studied the effect of thieno[2,3-d]-pyrimidine derivative TPY1 on TSH-stimulated synthesis of thyroid hormones in the culture of FRTL-5 thyrocytes and on thyroliberin-stimulated production of thyroid hormones in rat blood. Preincubation of FRTL-5 cells with TPY1 suppressed the stimulatory effect of TSH on the synthesis of thyroxine and triiodothyronine. Intraperitoneal injection of TPY1 in a dose of 25 mg/kg reduced thyroliberin-stimulated levels of thyroid hormones in the blood and inhibited the expression of genes encoding thyroid peroxidase, thyroglobulin, and Na+/I— cotransporter responsible for thyroxine synthesis. In the absence of thyroliberin stimulation, TPY1 did not affect the levels of thyroid hormones and expression of thyroidogenesis genes. Thus, a new TPY1 antagonist of TSH receptor can be a prototype of a drug for the treatment of autoimmune hyperthyroidism.

AB - The development of low-molecular-weight antagonists of thyroid-stimulating hormone (TSH) receptor is a promising trend in the treatment of autoimmune hyperthyroidism. We studied the effect of thieno[2,3-d]-pyrimidine derivative TPY1 on TSH-stimulated synthesis of thyroid hormones in the culture of FRTL-5 thyrocytes and on thyroliberin-stimulated production of thyroid hormones in rat blood. Preincubation of FRTL-5 cells with TPY1 suppressed the stimulatory effect of TSH on the synthesis of thyroxine and triiodothyronine. Intraperitoneal injection of TPY1 in a dose of 25 mg/kg reduced thyroliberin-stimulated levels of thyroid hormones in the blood and inhibited the expression of genes encoding thyroid peroxidase, thyroglobulin, and Na+/I— cotransporter responsible for thyroxine synthesis. In the absence of thyroliberin stimulation, TPY1 did not affect the levels of thyroid hormones and expression of thyroidogenesis genes. Thus, a new TPY1 antagonist of TSH receptor can be a prototype of a drug for the treatment of autoimmune hyperthyroidism.

KW - allosteric antagonist

KW - autoimmune hyperthyroidism

KW - thyroid hormone

KW - thyroid-stimulating hormone receptor

KW - thyroliberin

KW - Thyrotropin-Releasing Hormone

KW - Receptors, G-Protein-Coupled

KW - Graves Disease/drug therapy

KW - Rats

KW - Pyrimidines/pharmacology

KW - Animals

KW - Thyroxine/pharmacology

KW - Receptors, Thyrotropin/genetics

KW - Thyroid Hormones

KW - Thyrotropin

UR - http://www.scopus.com/inward/record.url?scp=85129826470&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/d523996b-b6ab-397a-946a-e5f6a69fe4d0/

U2 - 10.1007/s10517-022-05462-x

DO - 10.1007/s10517-022-05462-x

M3 - Article

C2 - 35501650

AN - SCOPUS:85129826470

VL - 172

SP - 713

EP - 717

JO - Bulletin of Experimental Biology and Medicine

JF - Bulletin of Experimental Biology and Medicine

SN - 0007-4888

IS - 6

ER -