Literature DB >> 24900217

Structure-Activity Study of Dihydrocinnamic Acids and Discovery of the Potent FFA1 (GPR40) Agonist TUG-469.

Elisabeth Christiansen1, Maria E Due-Hansen1, Christian Urban2, Nicole Merten3, Michael Pfleiderer4, Kasper K Karlsen1, Sanne S Rasmussen1, Mette Steensgaard1, Alexandra Hamacher2, Johannes Schmidt3, Christel Drewke3, Rasmus Koefoed Petersen5, Karsten Kristiansen5, Susanne Ullrich4, Evi Kostenis3, Matthias U Kassack2, Trond Ulven1.   

Abstract

The free fatty acid 1 receptor (FFA1 or GPR40), which is highly expressed on pancreatic β-cells and amplifies glucose-stimulated insulin secretion, has emerged as an attractive target for the treatment of type 2 diabetes. Several FFA1 agonists containing the para-substituted dihydrocinnamic acid moiety are known. We here present a structure-activity relationship study of this compound family suggesting that the central methyleneoxy linker is preferable for the smaller compounds, whereas the central methyleneamine linker gives higher potency to the larger compounds. The study resulted in the discovery of the potent and selective full FFA1 agonist TUG-469 (29).

Entities:  

Keywords:  Diabetes; FFA1; FFAR1; GPR40; drug discovery; fatty acids

Year:  2010        PMID： 24900217      PMCID： PMC4007913          DOI： 10.1021/ml100106c

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


  28 in total

1.  Ligand efficiency: a useful metric for lead selection.

Authors:  Andrew L Hopkins; Colin R Groom; Alexander Alex
Journal:  Drug Discov Today       Date:  2004-05-15       Impact factor: 7.851

2.  Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules.

Authors:  Celia P Briscoe; Andrew J Peat; Stephen C McKeown; David F Corbett; Aaron S Goetz; Thomas R Littleton; David C McCoy; Terry P Kenakin; John L Andrews; Carina Ammala; James A Fornwald; Diane M Ignar; Stephen Jenkinson
Journal:  Br J Pharmacol       Date:  2006-05-15       Impact factor: 8.739

3.  Synthesis and activity of small molecule GPR40 agonists.

Authors:  Dulce M Garrido; David F Corbett; Kate A Dwornik; Aaron S Goetz; Thomas R Littleton; Steve C McKeown; Wendy Y Mills; Terrence L Smalley; Celia P Briscoe; Andrew J Peat
Journal:  Bioorg Med Chem Lett       Date:  2006-01-24       Impact factor: 2.823

Review 4.  The long-chain fatty acid receptor, GPR40, and glucolipotoxicity: investigations using GPR40-knockout mice.

Authors:  Ruth Brownlie; Rachel M Mayers; Jackie A Pierce; Anna E Marley; David M Smith
Journal:  Biochem Soc Trans       Date:  2008-10       Impact factor: 5.407

5.  GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo.

Authors:  Martin G Latour; Thierry Alquier; Elizabeth Oseid; Caroline Tremblay; Thomas L Jetton; Jian Luo; Daniel C-H Lin; Vincent Poitout
Journal:  Diabetes       Date:  2007-04       Impact factor: 9.461

Review 6.  Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients.

Authors:  Petrine Wellendorph; Lars Dan Johansen; Hans Bräuner-Osborne
Journal:  Mol Pharmacol       Date:  2009-06-01       Impact factor: 4.436

7.  Discovery of 5-aryloxy-2,4-thiazolidinediones as potent GPR40 agonists.

Authors:  Changyou Zhou; Cheng Tang; Eric Chang; Min Ge; Songnian Lin; Eric Cline; Carina P Tan; Yue Feng; Yun-Ping Zhou; George J Eiermann; Aleksandr Petrov; Gino Salituro; Peter Meinke; Ralph Mosley; Taro E Akiyama; Monica Einstein; Sanjeev Kumar; Joel Berger; Andrew D Howard; Nancy Thornberry; Sander G Mills; Lihu Yang
Journal:  Bioorg Med Chem Lett       Date:  2009-10-15       Impact factor: 2.823

8.  Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes.

Authors:  Elisabeth Christiansen; Christian Urban; Nicole Merten; Kathrin Liebscher; Kasper K Karlsen; Alexandra Hamacher; Andreas Spinrath; Andrew D Bond; Christel Drewke; Susanne Ullrich; Matthias U Kassack; Evi Kostenis; Trond Ulven
Journal:  J Med Chem       Date:  2008-11-27       Impact factor: 7.446

9.  Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion.

Authors:  Sara Edfalk; Pär Steneberg; Helena Edlund
Journal:  Diabetes       Date:  2008-06-02       Impact factor: 9.461

10.  Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice.

Authors:  Kae Nagasumi; Ritsuko Esaki; Kimihiko Iwachidow; Yoshitaka Yasuhara; Kazuhiro Ogi; Hideyuki Tanaka; Mitsugu Nakata; Takashi Yano; Kozo Shimakawa; Shigehisa Taketomi; Koji Takeuchi; Hiroyuki Odaka; Yoshihiko Kaisho
Journal:  Diabetes       Date:  2009-05       Impact factor: 9.461
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  21 in total

1.  Design and Synthesis of Novel, Selective GPR40 AgoPAMs.

Authors:  Christopher W Plummer; Matthew J Clements; Helen Chen; Murali Rajagopalan; Hubert Josien; William K Hagmann; Michael Miller; Maria E Trujillo; Melissa Kirkland; Daniel Kosinski; Joel Mane; Michele Pachanski; Boonlert Cheewatrakoolpong; Andrew F Nolting; Robert Orr; Melodie Christensen; Louis-Charles Campeau; Michael J Wright; Randal Bugianesi; Sarah Souza; Xiaoping Zhang; Jerry Di Salvo; Adam B Weinglass; Richard Tschirret-Guth; Ravi Nargund; Andrew D Howard; Steven L Colletti
Journal:  ACS Med Chem Lett       Date:  2017-01-23       Impact factor: 4.345

2.  Structure-Activity Relationship of Novel and Selective Biaryl-Chroman GPR40 AgoPAMs.

Authors:  Helen Y Chen; Christopher W Plummer; Dong Xiao; Harry R Chobanian; Duane DeMong; Michael Miller; Maria E Trujillo; Melissa Kirkland; Daniel Kosinski; Joel Mane; Michele Pachanski; Boonlert Cheewatrakoolpong; Jerry Di Salvo; Brande Thomas-Fowlkes; Sarah Souza; Daniel A Tatosian; Qing Chen; Michael J Hafey; Robert Houle; Andrew F Nolting; Robert Orr; Juliann Ehrhart; Adam B Weinglass; Richard Tschirret-Guth; Andrew D Howard; Steven L Colletti
Journal:  ACS Med Chem Lett       Date:  2018-06-14       Impact factor: 4.345

3.  Discovery of AM-6226: A Potent and Orally Bioavailable GPR40 Full Agonist That Displays Efficacy in Nonhuman Primates.

Authors:  Sean P Brown; Paul Dransfield; Marc Vimolratana; Liusheng Zhu; Jian Luo; Jane Zhang; XianYun Jiao; Vatee Pattaropong; Simon Wong; Run Zhuang; Gayathri Swaminath; Jonathan B Houze; Daniel C-H Lin
Journal:  ACS Med Chem Lett       Date:  2018-06-06       Impact factor: 4.345

4.  Discovery of DS-1558: A Potent and Orally Bioavailable GPR40 Agonist.

Authors:  Rieko Takano; Masao Yoshida; Masahiro Inoue; Takeshi Honda; Ryutaro Nakashima; Koji Matsumoto; Tatsuya Yano; Tsuneaki Ogata; Nobuaki Watanabe; Masakazu Hirouchi; Tomoko Yoneyama; Shuichiro Ito; Narihiro Toda
Journal:  ACS Med Chem Lett       Date:  2015-01-13       Impact factor: 4.345

Review 5.  Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4.

Authors:  G Milligan; E Alvarez-Curto; K R Watterson; T Ulven; B D Hudson
Journal:  Br J Pharmacol       Date:  2015-02-27       Impact factor: 8.739

6.  Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists.

Authors:  Xiaohui Du; Paul J Dransfield; Daniel C-H Lin; Simon Wong; Yingcai Wang; Zhongyu Wang; Todd Kohn; Ming Yu; Sean P Brown; Marc Vimolratana; Liusheng Zhu; An-Rong Li; Yongli Su; Xianyun Jiao; Jiwen Jim Liu; Gayathri Swaminath; Thanhvien Tran; Jian Luo; Run Zhuang; Jane Zhang; Qi Guo; Frank Li; Richard Connors; Julio C Medina; Jonathan B Houze
Journal:  ACS Med Chem Lett       Date:  2014-02-03       Impact factor: 4.345

7.  Discovery of AM-1638: A Potent and Orally Bioavailable GPR40/FFA1 Full Agonist.

Authors:  Sean P Brown; Paul J Dransfield; Marc Vimolratana; XianYun Jiao; Liusheng Zhu; Vatee Pattaropong; Ying Sun; Jinqian Liu; Jian Luo; Jane Zhang; Simon Wong; Run Zhuang; Qi Guo; Frank Li; Julio C Medina; Gayathri Swaminath; Daniel C-H Lin; Jonathan B Houze
Journal:  ACS Med Chem Lett       Date:  2012-08-15       Impact factor: 4.345

8.  SAR Studies of Indole-5-propanoic Acid Derivatives To Develop Novel GPR40 Agonists.

Authors:  Dong-Oh Yoon; Xiaodi Zhao; Dohyun Son; Jung Tae Han; Jaesook Yun; Dongyun Shin; Hyun-Ju Park
Journal:  ACS Med Chem Lett       Date:  2017-11-21       Impact factor: 4.345

9.  In vitro and mouse in vivo characterization of the potent free fatty acid 1 receptor agonist TUG-469.

Authors:  C Urban; A Hamacher; H J Partke; M Roden; S Schinner; E Christiansen; M E Due-Hansen; T Ulven; H Gohlke; M U Kassack
Journal:  Naunyn Schmiedebergs Arch Pharmacol       Date:  2013-07-17       Impact factor: 3.000

10.  Indomethacin treatment prevents high fat diet-induced obesity and insulin resistance but not glucose intolerance in C57BL/6J mice.

Authors:  Even Fjære; Ulrike L Aune; Kristin Røen; Alison H Keenan; Tao Ma; Kamil Borkowski; David M Kristensen; Guy W Novotny; Thomas Mandrup-Poulsen; Brian D Hudson; Graeme Milligan; Yannan Xi; John W Newman; Fawaz G Haj; Bjørn Liaset; Karsten Kristiansen; Lise Madsen
Journal:  J Biol Chem       Date:  2014-04-17       Impact factor: 5.157
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