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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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References

    1. Albi E, Perrella G, Lazzarini A, Cataldi S, Lazzarini R, Floridi A, Ambesi-Impiombato FS, Curcio F. Critical role for the protons in FRTL-5 thyroid cells: nuclear sphingomyelinase induced-damage. Int. J. Mol. Sci. 2014;15(7):11 555-11 565. doi: 10.3390/ijms150711555
    1. Bakhtyukov AA, Derkach KV, Gureev MA, Dar’in DV, Sorokoumov VN, Romanova IV, Morina IY, Stepochkina AM, Shpakov AO. Comparative study of the steroidogenic effects of human chorionic gonadotropin and thieno[2,3-d]pyrimidinebased allosteric agonist of luteinizing hormone receptor in young adult, aging and diabetic male rats. Int. J. Mol. Sci. 2020;21(20):7493. doi: https://doi.org/10.3390/ijms21207493
    1. Derkach KV, Bakhtyukov AA, Sorokoumov VN, Shpakov AO. New thieno-[2,3-d]pyrimidine-based functional antagonist for the receptor of thyroid stimulating hormone. Dokl. Biochem. Biophys. 2020;491(1):77-80. doi: https://doi.org/10.1134/S1607672920020064 - DOI - PubMed
    1. Derkach KV, Bogush IV, Berstein LM, Shpakov AO. The influence of intranasal insulin on hypothalamic-pituitarythyroid axis in normal and diabetic rats. Horm. Metab. Res. 2015;47(12):916-924. doi: https://doi.org/10.1055/s-0035-1547236 - DOI - PubMed
    1. Dong YH, Fu DG. Autoimmune thyroid disease: mechanism, genetics and current knowledge. Eur. Rev. Med. Pharmacol. Sci. 2014;18(23):3611-3618. - PubMed

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