Recent developments in the discovery of FFA1 receptor agonists as novel oral treatment for type 2 diabetes mellitus

被引:95
作者
Defossa, Elisabeth [1 ]
Wagner, Michael [2 ]
机构
[1] Sanofi Deutsch GmbH, Lead Generat Candidate Realizat, D-65926 Frankfurt, Germany
[2] Sanofi Deutsch GmbH, Diabet Div, D-65926 Frankfurt, Germany
关键词
Type; 2; diabetes; Oral antidiabetics; GPR40; FFA1; GPCRs; INSULIN-SECRETION; GPR40; AGONIST; DOUBLE-BLIND; GLP-1; SECRETION; FATTY-ACIDS; POTENT; TAK-875; IDENTIFICATION; FFA1/GPR40; ACTIVATION;
D O I
10.1016/j.bmcl.2014.05.019
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Despite the availability of established medication for treatment of type 2 diabetes mellitus (T2DM) there still remains a significant unmet need for new effective, oral antidiabetic agents that improve glycemic control while maintaining an excellent safety profile. In this regard the FFA1 receptor has emerged as an attractive target in recent years. Activation of the FFA1 receptor has been shown to not only amplify glucose induced insulin secretion from pancreatic beta cells but also to stimulate incretin secretion from intestinal endocrine cells. The current review highlights on the latest developments and clinical data from evolving research on the potential of FFA1 agonists as effective treatment for T2DM. (C) 2014 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
引用
收藏
页码:2991 / 3000
页数:10
相关论文
共 78 条
  • [1] Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes
    Ahren, Bo
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2009, 8 (05) : 369 - 385
  • [2] Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes
    Ahren, Bo
    [J]. EXPERT OPINION ON EMERGING DRUGS, 2008, 13 (04) : 593 - 607
  • [3] [Anonymous], 2011, NAT DIABETESFACTSHEE
  • [4] [Anonymous], 2012, JIANGS HENGR MED C P
  • [5] GPR40-induced insulin secretion by the novel agonist TAK-875: first clinical findings in patients with type 2 diabetes
    Araki, T.
    Hirayama, M.
    Hiroi, S.
    Kaku, K.
    [J]. DIABETES OBESITY & METABOLISM, 2012, 14 (03) : 271 - 278
  • [6] Discovery of AM-1638: A Potent and Orally Bioavailable GPR40/FFA1 Full Agonist
    Brown, Sean P.
    Dransfield, Paul J.
    Vimolratana, Marc
    Jiao, XianYun
    Zhu, Liusheng
    Pattaropong, Vatee
    Sun, Ying
    Liu, Jinqian
    Luo, Jian
    Zhang, Jane
    Wong, Simon
    Zhuang, Run
    Guo, Qi
    Li, Frank
    Medina, Julio C.
    Swaminath, Gayathri
    Lin, Daniel C. -H.
    Houze, Jonathan B.
    [J]. ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (09): : 726 - 730
  • [7] Activation of GPR40 as a Therapeutic Target for the Treatment of Type 2 Diabetes
    Burant, Charles F.
    [J]. DIABETES CARE, 2013, 36 : S175 - S179
  • [8] TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial
    Burant, Charles F.
    Viswanathan, Prabhakar
    Marcinak, John
    Cao, Charlie
    Vakilynejad, Majid
    Xie, Benhuai
    Leifke, Eckhard
    [J]. LANCET, 2012, 379 (9824) : 1403 - 1411
  • [9] Chen Y., 2013, 73 AM DIAB ASS CHIC
  • [10] Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes
    Christiansen, Elisabeth
    Hansen, Steffen V. F.
    Urban, Christian
    Hudson, Brian D.
    Wargent, Edward T.
    Grundmann, Manuel
    Jenkins, Laura
    Zaibi, Mohamed
    Stocker, Claire J.
    Ullrich, Susanne
    Kostenis, Evi
    Kassack, Matthias U.
    Milligan, Graeme
    Cawthorne, Michael A.
    Ulven, Trond
    [J]. ACS MEDICINAL CHEMISTRY LETTERS, 2013, 4 (05): : 441 - 445