CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models
Background/Aim. Thyroid hormone receptor-β (THR-β) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR-β agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders. Materials and...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2023/4950597 |
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| author | Shengjian Huang Zhou Deng Wei Wang Guoqiang Liao Yiru Zhao Hua Zhong Qian Zhang Jing Liu Xuhua Mao Beizhong Chen Desi Pan You Zhou |
| author_facet | Shengjian Huang Zhou Deng Wei Wang Guoqiang Liao Yiru Zhao Hua Zhong Qian Zhang Jing Liu Xuhua Mao Beizhong Chen Desi Pan You Zhou |
| author_sort | Shengjian Huang |
| collection | DOAJ |
| description | Background/Aim. Thyroid hormone receptor-β (THR-β) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR-β agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders. Materials and Methods. We evaluated in vitro and in vivo efficacy and/or safety of CS27109 along with MGL3196 (a phase III THR-β agonist). Results. CS27109 showed pronounced activity and selectivity to THR-β and favorable PK properties, which was equivalent to MGL3196. In the hamster model, animals treated with a high dose of CS27109 showed equivalent reductions in serum TC and LDL-c with groups treated with MGL3196. In the rat model, CS27109 and MGL3196 reduced serum ALT, TC, TG, LDL-c, liver weight ratio, and liver steatosis. CS27109 simultaneously decreased liver TG and TC, and MGL3196 additionally reduced AST. In the mouse model, CS27109 dose-dependently reduced serum AST, ALT, liver inflammation, and NAS score, and also downregulated TC, LDL-c, liver steatosis, and fibrosis, but not in a dose-dependent manner. MGL3196 revealed an equivalent effect with CS27109 in that model. CS27109 also exhibited tolerable toxicity to the heart. Conclusions. CS27109 shows comparative in vitro and in vivo efficacy with MGL3196, suggesting its potential therapeutic application in the treatment of MAFLD such as dyslipidemia and steatohepatitis. |
| format | Article |
| id | doaj-art-965baee155cb456599d83ebced1dd251 |
| institution | Kabale University |
| issn | 1687-8345 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-965baee155cb456599d83ebced1dd2512025-08-20T03:37:29ZengWileyInternational Journal of Endocrinology1687-83452023-01-01202310.1155/2023/4950597CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine ModelsShengjian Huang0Zhou Deng1Wei Wang2Guoqiang Liao3Yiru Zhao4Hua Zhong5Qian Zhang6Jing Liu7Xuhua Mao8Beizhong Chen9Desi Pan10You Zhou11Shenzhen Chipscreen Biosciences Co., Ltd.Shenzhen Chipscreen Biosciences Co., Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Chengdu Chipscreen Pharmaceutical Ltd.Shenzhen Chipscreen Biosciences Co., Ltd.Shenzhen Chipscreen Biosciences Co., Ltd.Background/Aim. Thyroid hormone receptor-β (THR-β) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR-β agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders. Materials and Methods. We evaluated in vitro and in vivo efficacy and/or safety of CS27109 along with MGL3196 (a phase III THR-β agonist). Results. CS27109 showed pronounced activity and selectivity to THR-β and favorable PK properties, which was equivalent to MGL3196. In the hamster model, animals treated with a high dose of CS27109 showed equivalent reductions in serum TC and LDL-c with groups treated with MGL3196. In the rat model, CS27109 and MGL3196 reduced serum ALT, TC, TG, LDL-c, liver weight ratio, and liver steatosis. CS27109 simultaneously decreased liver TG and TC, and MGL3196 additionally reduced AST. In the mouse model, CS27109 dose-dependently reduced serum AST, ALT, liver inflammation, and NAS score, and also downregulated TC, LDL-c, liver steatosis, and fibrosis, but not in a dose-dependent manner. MGL3196 revealed an equivalent effect with CS27109 in that model. CS27109 also exhibited tolerable toxicity to the heart. Conclusions. CS27109 shows comparative in vitro and in vivo efficacy with MGL3196, suggesting its potential therapeutic application in the treatment of MAFLD such as dyslipidemia and steatohepatitis.http://dx.doi.org/10.1155/2023/4950597 |
| spellingShingle | Shengjian Huang Zhou Deng Wei Wang Guoqiang Liao Yiru Zhao Hua Zhong Qian Zhang Jing Liu Xuhua Mao Beizhong Chen Desi Pan You Zhou CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models International Journal of Endocrinology |
| title | CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models |
| title_full | CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models |
| title_fullStr | CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models |
| title_full_unstemmed | CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models |
| title_short | CS27109, A Selective Thyroid Hormone Receptor-β Agonist Alleviates Metabolic-Associated Fatty Liver Disease in Murine Models |
| title_sort | cs27109 a selective thyroid hormone receptor β agonist alleviates metabolic associated fatty liver disease in murine models |
| url | http://dx.doi.org/10.1155/2023/4950597 |
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