Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia.
Institute of Chemistry, St. Petersburg State University, St. Petersburg, Russia.
Dokl Biochem Biophys. 2022 Apr;503(1):67-70. doi: 10.1134/S1607672922020016. Epub 2022 May 10.
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.
为了使因抗促甲状腺激素（TSH）而引起的甲状腺功能减退的甲状腺功能正常化，可以使用 TSH 受体的低分子量变构激动剂。一种新的化合物乙基-2-（4-（4-（5-氨基-6-（叔丁基羰基）-2-（甲硫基）噻吩并[2,3-d]嘧啶-4-基）苯基）-1H-1,2,3-三唑-1-基）乙酸酯（TPY3m），当给予大鼠时（25mg/kg，ip）刺激甲状腺素的产生，并且还增加了在培养的 FRTL-5 甲状腺细胞（30μM）和大鼠甲状腺中甲状腺生成基因的表达。TPY3m 的体外和体内处理不会导致甲状腺细胞中 TSH 受体基因的表达减少，在激素对受体的超激活条件下恢复其表达。这决定了当 TPY3m 与 TSH（FRTL-5）或促甲状腺素释放激素（大鼠）共同给予时，保留和在某些情况下增强 TSH 的甲状腺生成作用（FRTL-5）或促甲状腺素释放激素（大鼠）。TPY3m 是纠正亚临床甲状腺功能减退症甲状腺系统功能的原型药物。
