Derkach K V, Bakhtyukov A A, Sorokoumov V N, Shpakov A O
Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, 194223, St.-Petersburg, Russia.
Institute of Chemistry, St.-Petersburg State University, 198504, St.-Petersburg, Russia.
Dokl Biochem Biophys. 2020 Mar;491(1):77-80. doi: 10.1134/S1607672920020064. Epub 2020 Jun 1.
Thyroid stimulating hormone (TSH) receptor antagonists are required for the treatment of TSH-dependent tumors and Graves disease. We developed the compound 5-amino-N-(tert-butyl)-4-(4-iodophenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide (TP48) and showed that it reduces the TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Pretreatment of rats with compound TP48 (ip, 40 mg/kg) reduced the increase in the levels of total and free thyroxin in blood and the increase in the expression of thyroglobulin and D2 deiodinase genes in the thyroid gland, which are responsible for the synthesis of thyroid hormones, which were caused by intranasal administration of thyroliberin to animals (300 μg/kg). These data indicate that compound TP48 is a functional antagonist of the TSH receptor and can be used to correct the thyroid status in hyperthyroidism.
促甲状腺激素（TSH）受体拮抗剂是治疗TSH依赖性肿瘤和格雷夫斯病所必需的。我们研发了化合物5-氨基-N-（叔丁基）-4-（4-碘苯基）-2-（甲硫基）噻吩并[2,3-d]嘧啶-6-甲酰胺（TP48），并表明它可降低大鼠甲状腺膜中TSH刺激的腺苷酸环化酶活性。用化合物TP48（腹腔注射，40mg/kg）预处理大鼠，可降低动物经鼻给予促甲状腺素（300μg/kg）后血液中总甲状腺素和游离甲状腺素水平的升高，以及甲状腺中甲状腺球蛋白和D2脱碘酶基因表达的增加，这些基因负责甲状腺激素的合成。这些数据表明化合物TP48是TSH受体的功能性拮抗剂，可用于纠正甲状腺功能亢进的甲状腺状态。
