%0 Journal Article
%T The Study of Biological Activity of a New Thieno[2,3-D]-Pyrimidine-Based Neutral Antagonist of Thyrotropin Receptor.
%A Derkach KV
%A Fokina EA
%A Bakhtyukov AA
%A Sorokoumov VN
%A Stepochkina AM
%A Zakharova IO
%A Shpakov AO
%J Bull Exp Biol Med
%V 172
%N 6
%D Apr 2022
%M 35501650
%F 0.737
%R 10.1007/s10517-022-05462-x
%X 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.