A Duplexed high-throughput screen to identify allosteric modulators of the glucagon-like peptide 1 and glucagon receptors

Journal of Biomolecular Screening

Volumn 19, Issue 6, 2014, Pages 847-858

  Morris, Lindsey C ^a   Days, Emily L ^a   Turney, Maxine ^a   Mi, Dehui ^a   Lindsley, Craig W ^a   Weaver, C David ^a   Niswender, Kevin D ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Tennessee Valley Healthcare System   (United States)

Author keywords

agonist; calcium; glucagon like peptide 1 receptor; High throughput screening; positive allosteric modulator

Indexed keywords

CALCIUM; CYCLIC AMP; DYE; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCAGON RECEPTOR; UNCLASSIFIED DRUG; VU 0089276; VU 0109197; VU 0138721; VU 0143436; VU 056556; VU 0056556; EXENDIN 4; GLUCOSE; LIRAGLUTIDE; PEPTIDE; RECOMBINANT PROTEIN; VENOM;

ALLOSTERISM; ANIMAL CELL; ARTICLE; ASSAY; CALCIUM TRANSPORT; CELL LINE; CONTROLLED STUDY; EMBRYO; FEMALE; GENE OVEREXPRESSION; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; PROCESS OPTIMIZATION; SCREENING; WORKFLOW; AGONIST; CONCENTRATION RESPONSE; DRUG ACTIVITY; DRUG DESIGN; DRUG DETERMINATION; DRUG STRUCTURE; ANIMAL; BINDING SITE; CHEMISTRY; CHO CELL LINE; CRICETULUS; DISEASE COURSE; DRUG EFFECTS; HAMSTER; PROCEDURES; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; ANIMALS; BINDING SITES; CALCIUM; CELL LINE; CELL LINE, TUMOR; CHO CELLS; CRICETINAE; CRICETULUS; CYCLIC AMP; DISEASE PROGRESSION; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; LIRAGLUTIDE; PEPTIDES; RECEPTORS, GLUCAGON; RECOMBINANT PROTEINS; SIGNAL TRANSDUCTION; VENOMS;

EID: 84904860442     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057114520971     Document Type: Article

References (34)

1. Holst J. J.. The Physiology of Glucagon-Like Peptide 1. Physiol. Rev. 2007 ; 87 (4). 1409-1439 (Pubitemid 350041474)
2. Perry C. M.. Liraglutide: A Review of Its Use in the Management of Type 2 Diabetes Mellitus. Drugs. 2011 ; 71 (17). 2347-2373
3. Drucker D. J., Nauck M. A.. The Incretin System: Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes. Lancet. 2006 ; 368 (9548). 1696-1705 (Pubitemid 46048557)
4. Hansen K. B., Vilsboll T., Knop F. K.. Incretin Mimetics: A Novel Therapeutic Option for Patients with Type 2 Diabetes - a Review. Diab. Met. Synd. Obes. 2010 ; 3: 155-163
5. Edwards K. L., Stapleton M., Weis J., et al. An Update in Incretin-Based Therapy: A Focus on Glucagon-Like Peptide-1 Receptor Agonists. Diab. Tech. Therap. 2012 ; 14 (10). 951-967
6. Garber A. J.. Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Review of Their Efficacy and Tolerability. Diab. Care. 2011 ; 34: S279 - S284
7. Bode B. W., Testa M. A., Magwire M., et al. Patient-Reported Outcomes following Treatment with the Human GLP-1 Analogue Liraglutide or Glimepiride in Monotherapy: Results from a Randomized Controlled Trial in Patients with Type 2 Diabetes. Diab. Obes. Metab. 2010 ; 12 (7). 604-612
8. Lovshin J. A., Drucker D. J.. Incretin-Based Therapies for Type 2 Diabetes Mellitus. Nature Rev. Endocrinol. 2009 ; 5 (5). 262-269
9. Butler P. C., Elashoff M., Elashoff R., et al. A Critical Analysis of the Clinical Use of Incretin-Based Therapies: Are the GLP-1 Therapies Safe?. Diab. Care. 2013 ; 36 (7). 2118-2125
10. Kenakin T., Christopoulos A.. Signalling Bias in New Drug Discovery: Detection, Quantification and Therapeutic Impact. Nature Rev. Drug Disc. 2013 ; 12 (3). 205-216
11. Willard F. S., Sloop K. W.. Physiology and Emerging Biochemistry of the Glucagon-Like Peptide-1 Receptor. Exper. Diab. Res. 2012 ; 2012: 470851
12. Montrose-Rafizadeh C., Avdonin P., Garant M. J., et al. Pancreatic Glucagon-Like Peptide-1 Receptor Couples to Multiple G Proteins and Activates Mitogen-Activated Protein Kinase Pathways in Chinese Hamster Ovary Cells. Endocrinology. 1999 ; 140 (3). 1132-1140 (Pubitemid 29104213)
13. Sonoda N., Imamura T., Yoshizaki T., et al. Beta-Arrestin-1 Mediates Glucagon-Like Peptide-1 Signaling to Insulin Secretion in Cultured Pancreatic Beta Cells. Proc. Natl. Acad. Sci. USA. 2008 ; 105 (18). 6614-6619 (Pubitemid 351754555)
14. Buteau J., Roduit R., Susini S., et al. Glucagon-Like Peptide-1 Promotes DNA Synthesis, Activates Phosphatidylinositol 3-Kinase and Increases Transcription Factor Pancreatic and Duodenal Homeobox Gene 1 (PDX-1) DNA Binding Activity in Beta (INS-1)-Cells. Diabetologia. 1999 ; 42 (7). 856-864 (Pubitemid 29325077)
15. Koole C., Pabreja K., Savage E. E., et al. Recent Advances in Understanding GLP-1R (Glucagon-Like Peptide-1 Receptor) Function. Biochem. Soc. Trans. 2013 ; 41 (1). 172-179
16. Selway J., Rigatti R., Storey N., et al. Evidence That Ca2+ within the Microdomain of the L-Type Voltage Gated Ca2+ Channel Activates ERK in MIN6 Cells in Response to Glucagon-Like Peptide-1. PLoS One. 2012 ; 7 (3). e33004
17. Hoare S. R.. Allosteric Modulators of Class B G-Protein-Coupled Receptors. Curr. Neuropharmacol. 2007 ; 5 (3). 168-179 (Pubitemid 351863858)
18. Reiter E., Ahn S., Shukla A. K., et al. Molecular Mechanism of Beta-Arrestin-Biased Agonism at Seven-Transmembrane Receptors. Ann. Rev. Pharmacol. Toxicol. 2012 ; 52: 179-197
19. Hohmeier H. E., Mulder H., Chen G., et al. Isolation of INS-1-Derived Cell Lines with Robust ATP-Sensitive K+ Channel-Dependent and -Independent Glucose-Stimulated Insulin Secretion. Diabetes. 2000 ; 49 (3). 424-430 (Pubitemid 30131788)
20. Pantel J., Williams S. Y., Mi D. H., et al. Development of a High Throughput Screen for Allosteric Modulators of Melanocortin-4 Receptor Signaling Using a Real Time cAMP Assay. Euro. J. Pharmacol. 2011 ; 660 (1). 139-147
21. Noetzel M. J., Rook J. M., Vinson P. N., et al. Functional Impact of Allosteric Agonist Activity of Selective Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 in Regulating Central Nervous System Function. Mol. Pharmacol. 2012 ; 81 (2). 120-133
22. Shirey J. K., Xiang Z., Orton D., et al. An allosteric Potentiator of M4 mAChR Modulates Hippocampal Synaptic Transmission. Nat. Chem. Biol. 2008 ; 4 (1). 42-50 (Pubitemid 350273654)
23. Doyle M. E., Egan J. M.. Glucagon-Like Peptide-1. Recent Prog. Horm. Res. 2001 ; 56: 377-399
24. Zhang J. H., Chung T. D., Oldenburg K. R.. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays. J. Biomol. Screen. 1999 ; 4 (2). 67-73 (Pubitemid 29278954)
25. Koole C., Wootten D., Simms J., et al. Allosteric Ligands of the Glucagon-Like Peptide 1 Receptor (GLP-1R) Differentially Modulate Endogenous and Exogenous Peptide Responses in a Pathway-Selective Manner: Implications for Drug Screening. Molec. Pharmacol. 2010 ; 78 (3). 456-465
26. Eng H., Sharma R., McDonald T. S., et al. Demonstration of the Innate Electrophilicity Of 4-(3-(Benzyloxy)Phenyl)-2-(Ethylsulfinyl)-6- (Trifluoromethyl)Pyrimidine (BETP), a Small Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 (GLP-1) Receptor. Drug Metab. Dispos. 2013 ; 41 (8). 1470-1479
27. Coopman K., Huang Y., Johnston N., et al. Comparative Effects of the Endogenous Agonist Glucagon-Like Peptide-1 (GLP-1)-(7-36) Amide and the Small-Molecule Ago-Allosteric Agent "Compound 2" at the GLP-1 Receptor. J. Pharmacol. Exper. Therap. 2010 ; 334 (3). 795-808
28. Wootten D., Simms J., Koole C., et al. Modulation of the Glucagon-Like Peptide-1 Receptor Signaling by Naturally Occurring and Synthetic Flavonoids. J. Pharmacol. Exper. Therap. 2011 ; 336 (2). 540-550
29. Sloop K. W., Willard F. S., Brenner M. B., et al. Novel Small Molecule Glucagon-Like Peptide-1 Receptor Agonist Stimulates Insulin Secretion in Rodents and from Human Islets. Diabetes. 2010 ; 59 (12). 3099-3107
30. Knudsen L. B., Kiel D., Teng M., et al. Small-Molecule Agonists for the Glucagon-Like Peptide 1 Receptor. Proc. Natl. Acad. Sci. USA. 2007 ; 104 (3). 937-942 (Pubitemid 46154715)
31. Jorgensen R., Kubale V., Vrecl M., et al. Oxyntomodulin Differentially Affects Glucagon-Like Peptide-1 Receptor Beta-Arrestin Recruitment and Signaling through Galpha(s). J. Pharmacol. Exper. Therap. 2007 ; 322 (1). 148-154 (Pubitemid 46956350)
32. Wootten D., Savage E. E., Valant C., et al. Allosteric Modulation of Endogenous Metabolites as an Avenue for Drug Discovery. Mol. Pharmacol. 2012 ; 82 (2). 281-290
33. Sharma S., Kedrowski J., Rook J. M., et al. Discovery of Molecular Switches That Modulate Modes of Metabotropic Glutamate Receptor Subtype 5 (mGlu5) Pharmacology in Vitro and in Vivo within a Series of Functionalized, Regioisomeric 2- and 5-(Phenylethynyl)Pyrimidines. J. Med. Chem. 2009 ; 52 (14). 4103-4106
34. Wood M. R., Hopkins C. R., Brogan J. T., et al. "Molecular switches" on mGluR allosteric ligands that modulate modes of pharmacology. Biochemistry. 2011 ; 50 (13). 2403-2410