Discovery of a Potent and Selective GPR120 Agonist

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• 作者：Bharat Shimpukade ; Brian D. Hudson ; Christine Kiel Hovgaard ; Graeme Milligan ; Trond Ulven
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：May 10, 2012
• 年：2012
• 卷：55
• 期：9
• 页码：4511-4515
• 全文大小：242K
• 年卷期：v.55,no.9(May 10, 2012)
• ISSN：1520-4804

文摘

GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist.