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Literature DB >> 28105282

Discovery of Chromane Propionic Acid Analogues as Selective Agonists of GPR120 with in Vivo Activity in Rodents.

Gregory L Adams¹, Francisco Velazquez², Charles Jayne², Unmesh Shah², Shouwu Miao², Eric R Ashley², Maria Madeira², Taro E Akiyama², Jerry Di Salvo², Takao Suzuki³, Nengxue Wang³, Quang Truong², Eric Gilbert², Dan Zhou², Andreas Verras², Melissa Kirkland², Michele Pachanski², Maryann Powles², Wu Yin², Feroze Ujjainwalla², Srikanth Venkatraman², Scott D Edmondson².

Abstract

GPR120 (FFAR4) is a fatty acid sensing G protein coupled receptor (GPCR) that has been identified as a target for possible treatment of type 2 diabetes. A selective activator of GPR120 containing a chromane scaffold has been designed, synthesized, and evaluated in vivo. Results of these efforts suggest that chromane propionic acid 18 is a suitable tool molecule for further animal studies. Compound 18 is selective over the closely related target GPR40 (FFAR1), has a clean off-target profile, demonstrates suitable pharmacokinetic properties, and has been evaluated in wild-type/knockout GPR120 mouse oGTT studies.

Entities: Chemical Disease Gene Species

Keywords: FFAR4; GPR120; chromane; insulin sensitization; type 2 diabetes

Year: 2016 PMID： 28105282 PMCID： PMC5238488 DOI： 10.1021/acsmedchemlett.6b00394

Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345

24 in total

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Journal: Neuron Date: 2000-04 Impact factor: 17.173

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Authors: Satoshi Miyauchi; Akira Hirasawa; Tomoyo Iga; Ning Liu; Chisato Itsubo; Keiko Sadakane; Takafumi Hara; Gozoh Tsujimoto
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Authors: Graeme Milligan; Bharat Shimpukade; Trond Ulven; Brian D Hudson
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Authors: Da Young Oh; Saswata Talukdar; Eun Ju Bae; Takeshi Imamura; Hidetaka Morinaga; WuQiang Fan; Pingping Li; Wendell J Lu; Steven M Watkins; Jerrold M Olefsky
Journal: Cell Date: 2010-09-03 Impact factor: 41.582

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Authors: P Zimmet; K G Alberti; J Shaw
Journal: Nature Date: 2001-12-13 Impact factor: 49.962

Review 6. Targeting GPR120 and other fatty acid-sensing GPCRs ameliorates insulin resistance and inflammatory diseases.

Authors: Saswata Talukdar; Jerrold M Olefsky; Olivia Osborn
Journal: Trends Pharmacol Sci Date: 2011-06-12 Impact factor: 14.819

Review 7. Free fatty acid receptor agonists for the treatment of type 2 diabetes: drugs in preclinical to phase II clinical development.

Authors: Zheng Li; Qianqian Qiu; Xinqian Geng; Jianyong Yang; Wenlong Huang; Hai Qian
Journal: Expert Opin Investig Drugs Date: 2016-05-27 Impact factor: 6.206

Review 8. Potential roles of GPR120 and its agonists in the management of diabetes.

Authors: Dan Zhang; Po Sing Leung
Journal: Drug Des Devel Ther Date: 2014-07-29 Impact factor: 4.162

9. GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans.

Authors: Virginia M Stone; Shalinee Dhayal; Katy J Brocklehurst; Carol Lenaghan; Maria Sörhede Winzell; Mårten Hammar; Xiufeng Xu; David M Smith; Noel G Morgan
Journal: Diabetologia Date: 2014-03-25 Impact factor: 10.122

10. A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice.

Authors: Da Young Oh; Evelyn Walenta; Taro E Akiyama; William S Lagakos; Denise Lackey; Ariane R Pessentheiner; Roman Sasik; Nasun Hah; Tyler J Chi; Jason M Cox; Mary Ann Powels; Jerry Di Salvo; Christopher Sinz; Steven M Watkins; Aaron M Armando; Heekyung Chung; Ronald M Evans; Oswald Quehenberger; Joanne McNelis; Juliane G Bogner-Strauss; Jerrold M Olefsky
Journal: Nat Med Date: 2014-07-06 Impact factor: 87.241

7 in total

1. Discovery of an Isothiazole-Based Phenylpropanoic Acid GPR120 Agonist as a Development Candidate for Type 2 Diabetes.

Authors: Xuqing Zhang; Chaozhong Cai; Zhihua Sui; Mark Macielag; Yuanping Wang; Wen Yan; Arthur Suckow; Hong Hua; Austin Bell; Peter Haug; Wilma Clapper; Celia Jenkinson; Joseph Gunnet; James Leonard; William V Murray
Journal: ACS Med Chem Lett Date: 2017-07-27 Impact factor: 4.345

2. GPR120/FFAR4 Pharmacology: Focus on Agonists in Type 2 Diabetes Mellitus Drug Discovery.

Authors: Gabriele Carullo; Sarah Mazzotta; Margarita Vega-Holm; Fernando Iglesias-Guerra; José Manuel Vega-Pérez; Francesca Aiello; Antonella Brizzi
Journal: J Med Chem Date: 2021-04-10 Impact factor: 7.446

3. The acute glucose lowering effect of specific GPR120 activation in mice is mainly driven by glucagon-like peptide 1.

Authors: Linda Sundström; Susanna Myhre; Monika Sundqvist; Andrea Ahnmark; William McCoull; Piotr Raubo; Sam D Groombridge; Magnus Polla; Ann-Christin Nyström; Lisbeth Kristensson; Mats Någård; Maria Sörhede Winzell
Journal: PLoS One Date: 2017-12-05 Impact factor: 3.240