AUTHOR=Lin Suwen , Huang Shengjian , Deng Zhou , Zhang Yu , Huang Lin , Wu Yanyi , Lv Shuyan , Wang Zhiyi , Huang Ning , Wang Lan , Chen Ziqi , Yu Guangyin , Yin Weihua , Zhou You , Fang Zhengyu 

TITLE=Discovery of a novel, liver-targeted thyroid hormone receptor-β agonist, CS271011, in the treatment of lipid metabolism disorders

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1109615

DOI=10.3389/fendo.2023.1109615

ISSN=1664-2392

ABSTRACT=Thyroid hormone receptor β plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, we discovered CS271011, a novel THR-β agonist with higher activation of THR-β in vitro and similar effects with MGL-3196 in vivo, a phase III THR-β agonist for treating hyperlipidaemia and non-alcoholic steatohepatitis. CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, we observed that CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. In conclusion, CS271011 is a potent and liver-targeted THR-β agonist for treating lipid metabolism disorders.