Structure-activity study of dihydrocinnamic acids and discovery of the potent FFA1 (GPR40) agonist TUG-469

ACS Medicinal Chemistry Letters

Volumn 1, Issue 7, 2010, Pages 345-349

  Christiansen, Elisabeth ^a   Due Hansen, Maria E ^a   Urban, Christian ^b   Merten, Nicole ^c   Pfleiderer, Michael ^d   Karlsen, Kasper K ^a   Rasmussen, Sanne S ^a   Steensgaard, Mette ^a   Hamacher, Alexandra ^b   Schmidt, Johannes ^c   Drewke, Christel ^c   Petersen, Rasmus Koefoed ^e   Kristiansen, Karsten ^e   Ullrich, Susanne ^d   Kostenis, Evi ^c   Kassack, Matthias U ^b   Ulven, Trond ^a  

^a UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^b HEINRICH HEINE UNIVERSITY   (Germany)

^c UNIVERSITY OF BONN   (Germany)

^d UNIVERSITY OF TÜBINGEN   (Germany)

^e UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

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

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; DIHYDROCINNAMIC ACID DERIVATIVE; G PROTEIN COUPLED RECEPTOR 40; G PROTEIN COUPLED RECEPTOR 40 STIMULATING AGENT; GLUCOSE; HYDROCINNAMIC ACID DERIVATIVE; LINOLEIC ACID; ROSIGLITAZONE; TUG 469; UNCLASSIFIED DRUG;

ARTICLE; CONCENTRATION RESPONSE; DRUG SYNTHESIS; INSULIN RELEASE; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 77958099021     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml100106c     Document Type: Article

References (30)

1. International Diabetes Federation. The Diabetes Atlas, 4 th ed.; October, 2009; http://www.diabetesatlas.org.
2. Unwin, N.; Gan, D.; Whiting, D. The IDF Diabetes Atlas: Providing evidence, raising awareness and promoting action Diabetes Res. Clin. Pract. 2010, 87, 2-3
3. The name FFA1 is designated by the International Union of Basic and Clinical Pharmacology to the receptor previously called GPR40 (http://www.iuphar.org/).
4. 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. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40 Nature 2003, 422, 173-176
5. Briscoe, C. P.; Tadayyon, M.; Andrews, J. L.; Benson, W. G.; Chambers, J. K.; Eilert, M. M.; Ellis, C.; Elshourbagy, N. A.; Goetz, A. S.; Minnick, D. T.; Murdock, P. R.; Sauls, H. R.; Shabon, U.; Spinage, L. D.; Strum, J. C.; Szekeres, P. G.; Tan, K. B.; Way, J. M.; Ignar, D. M.; Wilson, S.; Muir, A. I. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids J. Biol. Chem. 2003, 278, 11303-11311
6. Kotarsky, K.; Nilsson, N. E.; Flodgren, E.; Owman, C.; Olde, B. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs Biochem. Biophys. Res. Commun. 2003, 301, 406-410
7. Edfalk, S.; Steneberg, P.; Edlund, H. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion Diabetes 2008, 57, 2280-2287
8. Stoddart, L. A.; Smith, N. J.; Milligan, G. International Union of Pharmacology. LXXI. Free Fatty Acid Receptors FFA1,-2, and-3: Pharmacology and Pathophysiological Functions Pharmacol. Rev. 2008, 60, 405-417
9. Wellendorph, P.; Johansen, L. D.; Brauner-Osborne, H. Molecular Pharmacology of Promiscuous Seven Transmembrane Receptors Sensing Organic Nutrients Mol. Pharmacol. 2009, 76, 453-465
10. Newgard, C. B.; McGarry, J. D. Metabolic coupling factors in pancreatic β-cell signal transduction Annu. Rev. Biochem. 1995, 64, 689-719
11. Steneberg, R.; Rubins, N.; Bartoov-Shifman, R.; Walker, M. D.; Edlund, H. The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse Cell Metab. 2005, 1, 245-258
12. Brownlie, R.; Mayers, R. M.; Pierce, J. A.; Marley, A. E.; Smith, D. M. The long-chain fatty acid receptor, GPR40, and glucolipotoxicity: Investigations using GPR40-knockout mice Biochem. Soc. Trans. 2008, 36, 950-954
13. Latour, M. G.; Alquier, T.; Oseid, E.; Tremblay, C.; Jetton, T. L.; Luo, J.; Lin, D. C. H.; Poitout, V. GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo Diabetes 2007, 56, 1087-1094
14. Kebede, M.; Alquier, T.; Latour, M. G.; Semache, M.; Tremblay, C.; Poitout, V. The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding Diabetes 2008, 57, 2432-2437
15. Tan, C. P.; Feng, Y.; Zhou, Y. P.; Eiermann, G. J.; Petrov, A.; Zhou, C. Y.; Lin, S. N.; Salituro, G.; Meinke, P.; Mosley, R.; Akiyama, T. E.; Einstein, M.; Kumar, S.; Berger, J. P.; Mills, S. G.; Thornberry, N. A.; Yang, L. H.; Howard, A. D. Selective small-molecule agonists of G protein-coupled receptor 40 promote glucose-dependent insulin secretion and reduce blood glucose in mice Diabetes 2008, 57, 2211-2219
16. Nagasumi, K.; Esaki, R.; Iwachidow, K.; Yasuhara, Y.; Ogi, K.; Tanaka, H.; Nakata, M.; Yano, T.; Shimakawa, K.; Taketomi, S.; Takeuchi, K.; Odaka, H.; Kaisho, Y. Overexpression of GPR40 in Pancreatic beta-Cells Augments Glucose-Stimulated Insulin Secretion and Improves Glucose Tolerance in Normal and Diabetic Mice Diabetes 2009, 58, 1067-1076
17. Lan, H.; Hoos, L. M.; Liu, L.; Tetzloffl, G.; Hu, W. W.; Abbondanzo, S. J.; Vassileva, G.; Gustafson, E. L.; Hedrick, J. A.; Davis, H. R. Lack of FFAR1/GPR40 Does Not Protect Mice From High-Fat Diet-Induced Metabolic Disease Diabetes 2008, 57, 2999-3006
18. Alquier, T.; Peyot, M. L.; Latour, M. G.; Kebede, M.; Sorensen, C. M.; Gesta, S.; Kahn, C. R.; Smith, R. D.; Jetton, T. L.; Metz, T. O.; Prentki, M.; Poitout, V. Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets Diabetes 2009, 58, 2607-2615
19. Briscoe, C. P.; Peat, A. J.; McKeown, S. C.; Corbett, D. F.; Goetz, A. S.; Littleton, T. R.; McCoy, D. C.; Kenakin, T. P.; Andrews, J. L.; Ammala, C.; Fornwald, J. A.; Ignar, D. M.; Jenkinson, S. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: Identification of agonist and antagonist small molecules Br. J. Pharmacol. 2006, 148, 619-628
20. Garrido, D. M.; Corbett, D. F.; Dwornik, K. A.; Goetz, A. S.; Littleton, T. R.; McKeown, S. C.; Mills, W. Y.; Smalley, T. L.; Briscoe, C. P.; Peat, A. J. Synthesis and activity of small molecule GPR40 agonists Bioorg. Med. Chem. Lett. 2006, 16, 1840-1845
21. McKeown, S. C.; Corbett, D. F.; Goetz, A. S.; Littleton, T. R.; Bigham, E.; Briscoe, C. P.; Peat, A. J.; Watson, S. P.; Hickey, D. M. B. Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor Bioorg. Med. Chem. Lett. 2007, 17, 1584-1589
22. Song, F. B.; Lu, S. F.; Gunnet, J.; Xu, J. Z.; Wines, P.; Proost, J.; Liang, Y.; Baumann, C.; Lenhard, J.; Murray, W. V.; Demarest, K. T.; Kuo, G. H. Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a novel series of G protein-coupled receptor 40 agonists J. Med. Chem. 2007, 50, 2807-2817
23. Christiansen, E.; Urban, C.; Merten, N.; Liebscher, K.; Karlsen, K. K.; Hamacher, A.; Spinrath, A.; Bond, A. D.; Drewke, C.; Ullrich, S.; Kassack, M. U.; Kostenis, E.; Ulven, T. 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 J. Med. Chem. 2008, 51, 7061-7064
24. Tikhonova, I. G.; Sum, C. S.; Neumann, S.; Engel, S.; Raaka, B. M.; Costanzi, S.; Gershengorn, M. C. Discovery of novel Agonists and antagonists of the free fatty acid receptor 1 (FFAR1) using virtual screening J. Med. Chem. 2008, 51, 625-633
25. Zhou, C. Y.; Tang, C.; Chang, E.; Ge, M.; Lin, S. N.; Cline, E.; Tan, C. P.; Feng, Y.; Zhou, Y. P.; Eiermann, G. J.; Petrov, A.; Salituro, G.; Meinke, P.; Mosley, R.; Akiyama, T. E.; Einstein, M.; Kumar, S.; Berger, J.; Howard, A. D.; Thornberry, N.; Mills, S. G.; Yang, L. H. Discovery of 5-aryloxy-2,4- thiazolidinediones as potent GPR40 agonists Bioorg. Med. Chem. Lett. 2010, 20, 1298-1301
26. Humphries, P. S.; Benbow, J. W.; Bonin, P. D.; Boyer, D.; Doran, S. D.; Frisbie, R. K.; Piotrowski, D. W.; Balan, G.; Bechle, B. M.; Conn, E. L.; Dirico, K. J.; Oliver, R. M.; Soeller, W. C.; Southers, J. A.; Yang, X. J. Synthesis and SAR of 1,2,3,4-tetrahydroisoquinolin-1-ones as novel G-protein-coupled receptor 40 (GPR40) antagonists Bioorg. Med. Chem. Lett. 2009, 19, 2400-2403
27. Bharate, S. B.; Nemmani, K. V. S.; Vishwakarma, R. A. Progress in the discovery and development of small-molecule modulators of G-protein-coupled receptor 40 (GPR40/FFA1/FFAR1): an emerging target for type 2 diabetes Expert Opin. Ther. Pat. 2009, 19, 237-264
28. Smith, N. J.; Stoddart, L. A.; Devine, N. M.; Jenkins, L.; Milligan, G. The Action and Mode of Binding of Thiazolidinedione Ligands at Free Fatty Acid Receptor 1 J. Biol. Chem. 2009, 284, 17527-17539
29. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: A useful metric for lead selection Drug Discovery Today 2004, 9, 430-431
30. Fang, Y.; Frutos, A. G.; Verklereen, R. Label-free cell-based assays for GPCR screening Comb. Chem. High Throughput Screening 2008, 11, 357-369