Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes

GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood...

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Autores principales:	Guoxia Ji, Qinghua Guo, Qidi Xue, Ruifang Kong, Shiben Wang, Kang Lei, Renmin Liu, Xuekun Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	GPR120 synthesis type 2 diabetes pharmacokinetic profiles Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/63131e8f92c846e99c5f3dfc66a20761
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spelling	oai:doaj.org-article:63131e8f92c846e99c5f3dfc66a207612021-11-25T18:28:21ZNovel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes10.3390/molecules262269071420-3049https://doaj.org/article/63131e8f92c846e99c5f3dfc66a207612021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6907https://doaj.org/toc/1420-3049GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound <b>11b</b> showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, <b>11b</b> showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound <b>11b</b> could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound <b>11b</b> might be a promising drug candidate for the treatment of T2DM.Guoxia JiQinghua GuoQidi XueRuifang KongShiben WangKang LeiRenmin LiuXuekun WangMDPI AGarticleGPR120synthesistype 2 diabetespharmacokinetic profilesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6907, p 6907 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GPR120 synthesis type 2 diabetes pharmacokinetic profiles Organic chemistry QD241-441
spellingShingle	GPR120 synthesis type 2 diabetes pharmacokinetic profiles Organic chemistry QD241-441 Guoxia Ji Qinghua Guo Qidi Xue Ruifang Kong Shiben Wang Kang Lei Renmin Liu Xuekun Wang Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
description	GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound <b>11b</b> showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, <b>11b</b> showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound <b>11b</b> could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound <b>11b</b> might be a promising drug candidate for the treatment of T2DM.
format	article
author	Guoxia Ji Qinghua Guo Qidi Xue Ruifang Kong Shiben Wang Kang Lei Renmin Liu Xuekun Wang
author_facet	Guoxia Ji Qinghua Guo Qidi Xue Ruifang Kong Shiben Wang Kang Lei Renmin Liu Xuekun Wang
author_sort	Guoxia Ji
title	Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
title_short	Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
title_full	Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
title_fullStr	Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
title_full_unstemmed	Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
title_sort	novel gpr120 agonists with improved pharmacokinetic profiles for the treatment of type 2 diabetes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/63131e8f92c846e99c5f3dfc66a20761
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Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes

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