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

被引:96
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
[31]  
Himmelsbach F., 2012, [No title captured], Patent No. [WO 2012/072691, 2012072691]
[32]   GLP-1 secretion is enhanced directly in the ileum but indirectly in the duodenum by a newly identified potent stimulator, zein hydrolysate, in rats [J].
Hira, Tohru ;
Mochida, Taisuke ;
Miyashita, Kyoko ;
Hara, Hiroshi .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2009, 297 (04) :G663-G671
[33]  
Houze JB, 2013, RSC DRUG DISCOV, V27, P403, DOI 10.1039/9781849735322-00403
[34]   AMG 837: A potent, orally bioavailable GPR40 agonist [J].
Houze, Jonathan B. ;
Zhu, Liusheng ;
Sun, Ying ;
Akerman, Michelle ;
Qiu, Wei ;
Zhang, Alex J. ;
Sharma, Rajiv ;
Schmitt, Michael ;
Wang, Yingcai ;
Liu, Jiwen ;
Liu, Jingian ;
Medina, Julio C. ;
Reagan, Jeff D. ;
Luo, Jian ;
Tonn, George ;
Zhang, Jane ;
Lu, Jenny Ying-Lin ;
Chen, Michael ;
Lopez, Edwin ;
Nguyen, Kathy ;
Yang, Li ;
Tang, Liang ;
Tian, Hui ;
Shuttleworth, Steven J. ;
Lin, Daniel C. -H. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (02) :1267-1270
[35]   A novel class of antagonists for the FFAs receptor GPR40 [J].
Hu, Hui ;
He, Ling Yan ;
Gong, Zhen ;
Li, Ning ;
Lu, Yi Na ;
Zhai, Qi Wei ;
Liu, Hong ;
Jiang, Hua Liang ;
Zhu, Wei Liang ;
Wang, He Yao .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 390 (03) :557-563
[36]   Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40 [J].
Itoh, Y ;
Kawamata, Y ;
Harada, M ;
Kobayashi, M ;
Fujii, R ;
Fukusumi, S ;
Ogi, K ;
Hosoya, M ;
Tanaka, Y ;
Uejima, H ;
Tanaka, H ;
Maruyama, M ;
Satoh, R ;
Okubo, S ;
Kizawa, H ;
Komatsu, H ;
Matsumura, F ;
Noguchi, Y ;
Shinobara, T ;
Hinuma, S ;
Fujisawa, Y ;
Fujino, M .
NATURE, 2003, 422 (6928) :173-176
[37]  
Jaganath M. R., 2011, ADA SAN DIEG 201 S1A, P60
[38]  
Kaku K., 2013, 49 EASD BARC SPAIN S
[39]   Randomized, Double-Blind, Dose-Ranging Study of TAK-875, a Novel GPR40 Agonist, in Japanese Patients With Inadequately Controlled Type 2 Diabetes [J].
Kaku, Kohei ;
Araki, Takahiro ;
Yoshinaka, Ryoji .
DIABETES CARE, 2013, 36 (02) :245-250
[40]   The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding [J].
Kebede, Melkam ;
Alquier, Thierry ;
Latour, Martin G. ;
Semache, Meriem ;
Tremblay, Caroline ;
Poitout, Vincent .
DIABETES, 2008, 57 (09) :2432-2437