Identification of a tetrahydroquinoline analog as a pharmacological inhibitor of the cAMP-binding protein Epac

Journal of Biological Chemistry

Volumn 287, Issue 53, 2012, Pages 44192-44202

  Courilleau, Delphine ^a   Bisserier, Malik ^b,d   Jullian, Jean Christophe ^c   Lucas, Alexandre ^b,d   Bouyssou, Pascal ^e   Fischmeister, Rodolphe ^a,f   Blondeau, Jean Paul ^a   Lezoualc'h, Frank ^b,d  

^a UNIVERSITÉ PARIS SACLAY   (France)

^b Université de Toulouse   (France)

^c CNRS   (France)

^d UNIVERSITÉ PAUL SABATIER   (France)

^e UNIVERSITÉ D'ORLÉANS   (France)

^f INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENERGIC RECEPTORS; BROMINE ATOMS; CARDIAC HYPERTROPHY; CELL-FREE SYSTEM; CULTURED CELL; FORMYL GROUP; GUANINE NUCLEOTIDES; HIGH-THROUGHPUT ASSAYS; INHIBITION MECHANISMS; INHIBITORY ACTIVITY; INTACT CELLS; ISOPRENALINE; PATHOPHYSIOLOGY; PHARMACOLOGICAL INHIBITORS; PROTEIN KINASE A; RELATED COMPOUNDS; STRUCTURE-ACTIVITY STUDIES; TETRAHYDROQUINOLINE; THERAPEUTIC DRUGS; THERAPEUTIC TARGETS; TUMOR INVASION;

BROMINE; DIAGNOSIS;

PROTEINS;

BROMINE; CE3F4; CYCLIC AMP BINDING PROTEIN; CYCLIC AMP DEPENDENT PROTEIN KINASE; EXCHANGE PROTEIN DIRECTLY ACTIVATED BY CAMP ISOFORM 1; HOLOENZYME; ISOPRENALINE; PROTEIN INHIBITOR; RAP1 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; ATOM; CELL FREE SYSTEM; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOWN REGULATION; DRUG DETERMINATION; DRUG EFFECT; DRUG MECHANISM; DRUG STRUCTURE; ENZYME ACTIVITY; HIGH THROUGHPUT SCREENING; IN VITRO STUDY; INHIBITION KINETICS; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; RAT; STRUCTURE ACTIVITY RELATION;

CARRIER PROTEINS; CYCLIC AMP; DRUG EVALUATION, PRECLINICAL; GUANINE NUCLEOTIDE EXCHANGE FACTORS; HEK293 CELLS; HUMANS; KINETICS; PROTEIN BINDING; QUINOLINES; RAP1 GTP-BINDING PROTEINS;

EID: 84871729159     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.422956     Document Type: Article

References (22)

1. Breckler, M., Berthouze, M., Laurent, A. C., Crozatier, B., Morel, E., and Lezoualc'h, F. (2011) Rap-linked cAMP signaling Epac proteins. Compartmentation, functioning and disease implications. Cell. Signal. 23, 1257-1266
2. Métrich, M., Berthouze, M., Morel, E., Crozatier, B., Gomez, A. M., and Lezoualc'h, F. (2010) Role of the cAMP-binding protein Epac in cardiovascular physiology and pathophysiology. Pflugers Arch. 459, 535-546
3. Kawasaki, H., Springett, G. M., Mochizuki, N., Toki, S., Nakaya, M., Matsuda, M., Housman, D. E., and Graybiel, A. M. (1998) A family of cAMP-binding proteins that directly activate Rap1. Science 282, 2275-2279
4. de Rooij, J., Zwartkruis, F. J., Verheijen, M. H., Cool, R. H., Nijman, S. M., Wittinghofer, A., and Bos, J. L. (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396, 474-477
5. Gloerich, M., and Bos, J. L. (2010) Epac. Defining a new mechanism for cAMP action. Annu. Rev. Pharmacol. Toxicol. 50, 355-375
6. Enserink, J. M., Christensen, A. E., de Rooij, J., van Triest, M., Schwede, F., Genieser, H. G., Døskeland, S. O., Blank, J. L., and Bos, J. L. (2002) A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat. Cell Biol. 4, 901-906
7. Zhong, N., and Zucker, R. S. (2005) cAMP acts on exchange protein activated by cAMP/cAMP-regulated guanine nucleotide exchange protein to regulate transmitter release at the crayfish neuromuscular junction. J. Neurosci. 25, 208-214
8. Tsalkova, T., Mei, F. C., and Cheng, X. (2012) A fluorescence-based high-throughput assay for the discovery of exchange protein directly activated by cyclic AMP (EPAC) antagonists. PLoS ONE 7, e30441
9. Chen, H., Tsalkova, T., Mei, F. C., Hu, Y., Cheng, X., and Zhou, J. (2012) 5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP. Bioorg. Med. Chem. Lett. 22, 4038-4043
10. Bouyssou, P., Le Goff, C., and Chenault, J. (1992) Synthesis of 7- and 5,7-substituted-6-fluoro-2-methyl-1,2,3,4-tetrahydroquinolines. Convenient precursors of quinolone antibacterial agents. J. Heterocyclic. Chem. 29, 895-898
11. Rehmann, H. (2006) Characterization of the activation of the Rap-specific exchange factor Epac by cyclic nucleotides. Methods Enzymol. 407, 159-173
12. van den Berghe, N., Cool, R. H., Horn, G., and Wittinghofer, A. (1997) Biochemical characterization of C3G. An exchange factor that discriminates between Rap1 and Rap2 and is not inhibited by Rap1A(S17N). Oncogene 15, 845-850
13. Jiang, L. I., Collins, J., Davis, R., Lin, K. M., DeCamp, D., Roach, T., Hsueh, R., Rebres, R. A., Ross, E. M., Taussig, R., Fraser, I., and Sternweis, P. C. (2007) Use of a cAMP BRET sensor to characterize a novel regulation of cAMP by the sphingosine 1-phosphate/G13 pathway. J. Biol. Chem. 282, 10576-10584
14. Wollert, K. C., Taga, T., Saito, M., Narazaki, M., Kishimoto, T., Glembotski, C. C., Vernallis, A. B., Heath, J. K., Pennica, D., Wood, W. I., and Chien, K. R. (1996) Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways. J. Biol. Chem. 271, 9535-9545
15. Métrich, M., Lucas, A., Gastineau, M., Samuel, J. L., Heymes, C., Morel, E., and Lezoualc'h, F. (2008) Epac mediates β-adrenergic receptor-induced cardiomyocyte hypertrophy. Circ. Res. 102, 959-965
16. Rehmann, H., Schwede, F., Døskeland, S. O., Wittinghofer, A., and Bos, J. L. (2003) Ligand-mediated activation of the cAMP-responsive guanine nucleotide exchange factor Epac. J. Biol. Chem. 278, 38548-38556
17. Das, R., Chowdhury, S., Mazhab-Jafari, M. T., Sildas, S., Selvaratnam, R., and Melacini, G. (2009) Dynamically driven ligand selectivity in cyclic nucleotide binding domains. J. Biol. Chem. 284, 23682-23696
18. de Rooij, J., Rehmann, H., van Triest, M., Cool, R. H., Wittinghofer, A., and Bos, J. L. (2000) Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J. Biol. Chem. 275, 20829-20836
19. Zhang, J. H., Chung, T. D., and Oldenburg, K. R. (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J. Biomol. Screen 4, 67-73
20. Cornish-Bowden, A. (1974) A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non-competitive inhibitors. Biochem. J. 137, 143-144
21. Christensen, A. E., Selheim, F., de Rooij, J., Dremier, S., Schwede, F., Dao, K. K., Martinez, A., Maenhaut, C., Bos, J. L., Genieser, H. G., and Døskeland, S. O. (2003) cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically to promote PC-12 cell neurite extension. J. Biol. Chem. 278, 35394-35402
22. Rangarajan, S., Enserink, J. M., Kuiperij, H. B., de Rooij, J., Price, L. S., Schwede, F., and Bos, J. L. (2003) Cyclic AMP induces integrin-mediated cell adhesion through Epac and Rap1 upon stimulation of the β 2-adrenergic receptor. J. Cell Biol. 160, 487-493