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

Naunyn-Schmiedeberg's Archives of Pharmacology

Volumn 386, Issue 12, 2013, Pages 1021-1030

  Urban, C ^a   Hamacher, A ^a   Partke, H J ^b   Roden, M ^b,c   Schinner, S ^c   Christiansen, E ^d   Due Hansen, M E ^d   Ulven, T ^d   Gohlke, H ^a   Kassack, M U ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b LEIBNIZ CENTER FOR DIABETES RESEARCH AT HEINRICH HEINE UNIVERSITY DÜSSELDORF   (Germany)

^c UNIVERSITY HOSPITAL DÜSSELDORF   (Germany)

^d UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

Diabetes; FFA1; Free fatty acids; GPR40; TUG 469

Indexed keywords

ANTIDIABETIC AGENT; CALCIUM ION; CYCLIC AMP; FASIGLIFAM; FORSKOLIN; G PROTEIN COUPLED RECEPTOR 120; G PROTEIN COUPLED RECEPTOR 40; GLUCOSE; GPR 120; GW 9508; INSULIN; RECOMBINANT G PROTEIN COUPLED RECEPTOR 40; RECOMBINANT PROTEIN; SERUM ALBUMIN; TGU 761; TUG 469; UNCLASSIFIED DRUG;

ALBUMIN BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIDIABETIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BLOOD GLUCOSE MONITORING; CALCIUM MOBILIZATION; CELL LINE; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG TISSUE LEVEL; GLUCOSE BLOOD LEVEL; GLUCOSE INTAKE; GLUCOSE TOLERANCE; GLUCOSE TOLERANCE TEST; IMPEDANCE; IN VITRO STUDY; IN VIVO STUDY; INSULIN BLOOD LEVEL; INSULIN RELEASE; INSULINOMA; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PARTIAL DRUG SYNTHESIS; PROTEIN EXPRESSION; RAT; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; TREATMENT OUTCOME;

ANILINE COMPOUNDS; ANIMALS; BIOLOGICAL MARKERS; BLOOD GLUCOSE; CALCIUM SIGNALING; CELL LINE, TUMOR; CYCLIC AMP; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HYPOGLYCEMIC AGENTS; INSULIN; INSULIN-SECRETING CELLS; MALE; METHYLAMINES; MICE; MICE, OBESE; PHENYLPROPIONATES; PREDIABETIC STATE; PROPIONATES; RATS; RECEPTORS, G-PROTEIN-COUPLED; RECOMBINANT PROTEINS; TIME FACTORS; TRANSFECTION;

EID: 84889887699     PISSN: 00281298     EISSN: 14321912     Source Type: Journal    
DOI: 10.1007/s00210-013-0899-3     Document Type: Article

References (30)

1. Briscoe CP, Peat AJ, McKeown SC, Corbett DF, Goetz AS, Littleton TR et al (2006) Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br J Pharmacol 148(5):619-628
2. Burant CF, Viswanathan P, Marcinak J, Cao C, Vakilynejad M, Xie B, et al (2012) TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 379(9824):1403-1411
3. Christiansen E, Urban C, Merten N, Liebscher K, Karlsen KK, Hamacher A et al (2008) 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 51(22):7061-7064
4. Christiansen E, Due-Hansen ME, Urban C, Merten N, Pfleiderer M, Karlsen KK et al (2010) Structure-activity study of dihydrocinnamic acids and discovery of the potent FFA1 (GPR40) agonist TUG-469. ACS Med Chem Lett 1(7):345-349
5. Christiansen E, Urban C, Grundmann M, Due-Hansen ME, Hagesaether E, Schmidt J et al (2011) Identification of a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with favorable physicochemical and in vitro ADME properties. J Med Chem 54(19):6691-6703
6. Christiansen E, Due-Hansen ME, Urban C, Grundmann M, Schroder R, Hudson BD et al (2012) Free fatty acid receptor 1 (FFA1/GPR40) agonists: mesylpropoxy appendage lowers lipophilicity and improves ADME properties. J Med Chem 55(14):6624-6628
7. Christiansen E, Due-Hansen ME, Urban C, Grundmann M, Schmidt J, Hansen SV, Hudson BD, Zaibi M, Markussen SB, Hagesaether E, Milligan G, Cawthorne MA, Kostenis E, Kassack MU, Ulven T (2013a) Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. J Med Chem 56(3):982-992
8. Christiansen E, Hansen SV, Urban C, Hudson BD, Wargent ET, Grundmann M, Jenkins L, Zaibi M, Stocker CJ, Ullrich S, Kostenis E, Kassack MU, Milligan G, Cawthorne MA, Ulven T (2013b) Discovery of TUG-770: A highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes. ACS Med Chem Lett 4(5):441-445
9. Doshi LS, Brahma MK, Sayyed SG, Dixit AV, Chandak PG, Pamidiboina V et al (2009) Acute administration of GPR40 receptor agonist potentiates glucose-stimulated insulin secretion in vivo in the rat. Metab Clin Exp 58(3):333-343
10. Edfalk S, Steneberg P, Edlund H (2008) GPR40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57:2280-2287
11. Feng DD, Luo ZQ, Roh SG, Hernandez M, Tawadros N, Keating DJ et al (2006) Reduction in voltage-gated K + currents in primary cultured rat pancreatic beta-cells by linoleic acids. Endocrinology 147(2):674-682
12. Garrido DM, Corbett DF, Dwornik KA, Goetz AS, Littleton TR, McKeown SC et al (2006) Synthesis and activity of small molecule GPR40 agonists. Bioorg Med Chem Lett 16(7):1840-1845
13. Gohlke H, Klebe G (2002) DrugScore meets CoMFA: adaptation of fields for molecular comparison (AFMoC) or how to tailor knowledge-based pair-potentials to a particular protein. J Med Chem 45(19):4153-4170
14. Hamacher A, Weigt M, Wiese M, Hoefgen B, Lehmann J, Kassack MU (2006) Dibenzazecine compounds with a novel dopamine/5HT2A receptor profile and 3D-QSAR analysis. BMC Pharmacol 6(11)
15. Holliday ND, Watson SJ, Brown AJ (2011) Drug discovery opportunities and challenges at g protein coupled receptors for long chain free Fatty acids. Front Endocrinol (Lausanne) 2:112. doi: 10.3389/fendo.2011.00112
16. Houze JB, Zhu L, Sun Y, Akerman M, Qiu W, Zhang AJ et al (2012) AMG 837: a potent, orally bioavailable GPR40 agonist. Bioorg Med Chem Lett 22(2):1267-1270
17. Hudson BD, Ulven T, Milligan G (2013) The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs. Curr Top Med Chem 13(1):14-25
18. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S et al (2003) Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 422(6928):173-176
19. Kassack MU, Hofgen B, Lehmann J, Eckstein N, Quillan JM, Sadee W (2002) Functional screening of g protein-coupled receptors by measuring intracellular calcium with a fluorescence microplate reader. J Biomol Screen 7(3):233-246
20. Kebede MA, Alquier T, Latour MG, Poitout V (2009) Lipid receptors and islet function: therapeutic implications? Diabetes Obes Metab 11:10-20
21. Lin DC, Zhang J, Zhuang R, Li F, Nguyen K, Chen M et al (2011) AMG 837: a novel GPR40/FFA1 agonist that enhances insulin secretion and lowers glucose levels in rodents. PLoS One 6(11):e27270
22. Luo J, Swaminath G, Brown SP, Zhang J, Guo Q, Chen M et al (2012) A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents. PLoS One 7(10):e46300
23. Nagasumi K, Esaki R, Iwachidow K, Yasuhara Y, Ogi K, Tanaka H et al (2009) Overexpression of GPR40 in pancreatic beta-cells augments glucose-stimulated insulin secretion and improves glucose tolerance in normal and diabetic mice (vol 58, pg 1067, 2009). Diabetes 58(7):1067-1076
24. Negoro N, Sasaki S, Mikami S, Ito M, Suzuki M, Tsujihata Y et al (2010) Discovery of TAK-875: a potent, selective, and orally bioavailable GPR40 agonist. ACS Med Chem Lett 1(6):290-294
25. Sasaki S, Kitamura S, Negoro N, Suzuki M, Tsujihata Y, Suzuki N et al (2011) Design, synthesis, and biological activity of potent and orally available G protein-coupled receptor 40 agonists. J Med Chem 54(5):1365-1378
26. Tikhonova IG, Sum CS, Neumann S, Thomas CJ, Raaka BM, Costanzi S et al (2007) Bidirectional, iterative approach to the structural delineation of the functional "Chemoprint" in GPR40 for agonist recognition. J Med Chem 50(13):2981-2989
27. Tsujihata Y, Ito R, Suzuki M, Harada A, Negoro N, Yasuma T et al (2011) TAK-875, an orally available G protein-coupled receptor 40/free fatty acid receptor 1 agonist, enhances glucose-dependent insulin secretion and improves both postprandial and fasting hyperglycemia in type 2 diabetic rats. J Pharmacol Exp Ther 339(1):228-237
28. Wagner R, Kaiser G, Gerst F, Christiansen E, Due-Hansen ME, Grundmann M, et al (2013) Reevaluation of fatty acid receptor 1 as a drug target for the stimulation of insulin secretion in humans. Diabetes 62(6):2106-2111
29. Zhou YP, Tan C, Eiermann G, Petrov A, Feng Y, Zhou CY et al (2008) Small molecule GPR40 agonists as glucose-dependent insulin secretion (GDIS) agents for the treatment of T2DM. Diabetes 57(8):2211-2219
30. Zhou CY, Tang C, Chang E, Ge M, Lin SN, Cline E et al (2010) Discovery of 5-aryloxy-2,4-thiazolidinediones as potent GPR40 agonists. Bioorg Med Chem Lett 20(3):1298-1301