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. 2022 Apr;172(6):713-717.
doi: 10.1007/s10517-022-05462-x. Epub 2022 May 2.

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

K V Derkach  1 , E A Fokina  1 , A A Bakhtyukov  1 , V N Sorokoumov  1 , A M Stepochkina  1 , I O Zakharova  1 , A O Shpakov  2
Affiliations

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

K V Derkach et al. Bull Exp Biol Med. 2022 Apr.

Abstract

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.

Keywords: allosteric antagonist; autoimmune hyperthyroidism; thyroid hormone; thyroid-stimulating hormone receptor; thyroliberin.

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