New Thieno-[2,3-d]pyrimidine-Based Functional Antagonist for the Receptor of Thyroid Stimulating Hormone

被引：12
作者：
Derkach, K. V. [1 ]
Bakhtyukov, A. A. [1 ]
Sorokoumov, V. N. [2 ]
Shpakov, A. O. [1 ]
机构：
[1] Russian Acad Sci, Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg 194223, Russia
[2] St Petersburg State Univ, Inst Chem, St Petersburg 198504, Russia
来源：
DOKLADY BIOCHEMISTRY AND BIOPHYSICS | 2020年 / 491卷 / 01期
基金：
俄罗斯科学基金会;
关键词：
thyroid stimulating hormone receptor; antagonist; thienopyrimidine; thyroid gland; THYROTROPIN RECEPTOR; TSH RECEPTOR; AGONISTS;
D O I：
10.1134/S1607672920020064
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 mu g/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.
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页码：77 / 80
页数：4
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