1. Hopkins, A.L. and Groom, C.R. The druggable genome. Nat. Rev. Drug Disc. 2002, 1:727-730.

2. Bockaert, J. and Pin, J.P Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J. 1999, 18:1723-1729.

3. Foord, S.M. Receptor classification: post genome. Curr. Opin. Pharmacol. 2002, 2:561-566.

4. Chalmers, D.T. and Behan, D.P. The use of constitutively active GPCRs in drug discovery and functional genomics. Nat. Rev. Drug Disc. 2002, 1:599- 608.

5. Vassilatis, D.K., Hohmann, J.G., Zeng, H., Li, F., Ranchalis, J.E., Mortrud, M.T., Brown, A., Rodriguez, S.S., Weller, J.R., Wright, A.C., Bergmann, J.E., Gaitanaris, G.A. The G protein-coupled receptor repertoires of human and mouse. Proc. Natl. Acad. Sci. USA 2003, 100:4903-4908.

6. Malbon, C.C. Frizzleds: new members of the superfamily of G protein-coupled receptors. Frontiers Biosci. 2004, 9:1048-1058.

7. Drews, J. Drug discovery: a historical perspective. Science 2000, 291:1960-1964.

8. Wise, A., Gearing, K., Rees, S. Target validation of G protein-coupled receptors. Drug Disc. Today 2002, 7:235-246.

9. Med Ad News Staff. World's best-selling medicines. Med Ad News 2004, 23:60-64.

10. NDC Health. The top 200 prescriptions for 2003 by number of U.S. prescriptions dispensed. RxList, 2003,

11. Schold, D. HIV co-receptors as targets for antiviral therapy. Curr. Top. Med. Chem. 2004, 4:883-893.

12. Kenakin, T. Predicting therapeutic value in the lead optimization phase of drug discovery. Nat. Rev. Drug Disc. 2003, 2:429-438.

13. Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J. Basic local alignment search tool. J. Mol. Biol. 1990, 215:403-410.

14. Altschul, S.F., Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, Z., Miller, W., Lipman, D.J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25:3389-3402.

15. Gaulton, A. and Attwood, T.K. Bioinformatics approaches for the classification of G protein-coupled receptors. Curr. Opin. Pharmacol. 2003, 3:114-120.

16. Takeda, S. Kadowaki, S., Haga, T., Takaesu, H., Mitaku, S. Identification of G proteincoupled receptor genes from the human genome sequence. FEBS Lett. 2002, 520:97-101.

17. Menzaghi, F., Behan, D.P., Chalmers, D.T. Constitutively activated G protein-coupled receptors: a novel approach to CNS drug discovery. Curr. Drug Targets CNS Neurol. Dis. 2002, 1:105-121.

18. Karchin, R., Karplus, K., Haussler, D. Classifying G protein-coupled receptors with support vector machines. Bioinformatics 2002, 18:147-159.

19. Krogh, A. Brown, M., Mian, I.S., Sjolander, K., Haussler, D. Hidden Markov models in computational biology: applications to protein modeling. J. Mol. Biol. 1994, 235:1501-1531.

20. O'Rourke, M.F., Iversen, L.J., Lomasney, J.W., Bylund, D.B. Species orthologs of the alpha-2A adrenergic receptor: the pharmacological properties of the bovine and rat receptors differ from the human and porcine receptors. J. Pharmacol. Exp. Ther. 1994, 271:735-740.

21. Lovenberg, T.W., Pyati, J., Chang, H., Wilson, S.J., Erlander, M.G. Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles. J. Pharmacol. Exp. Ther. 2000, 293:771-778.

22. Yao, B.B., Hutchins, C.W., Carr, T.L., Cassar, S., Masters, J.N., Bennani, Y.L., Esbenshade, T.A., Hancock, A.A. Molecular modeling and pharmacological analysis of species-related histamine H(3) receptor heterogeneity. Neuropharmacology 2003, 44:773-786.

23. Liu, C., Wilson, S.J., Kuei, C., Lovenberg, T.W.. Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J. Pharmacol. Exp. Ther. 2001, 299:121-130.

24. Schena, M., Shalon, D., Davis, R.W., Brown, P.O. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995, 270:467-470.

25. Liu, C., Ma, X., Jiang, X., Wilson, S.J., Hofstra, C.L., Blevitt, J., Pyati, J., Li, X., Chai, W., Carruthers, N., Lovenberg, T.W. Cloning and pharmacological characterization of a fourth histamine receptor (H4) expressed in bone marrow. Mol. Pharmacol. 2001, 59:420-426.

Borowsky, B., Adham, N., Jones, K.A., Raddatz, R., Artymyshyn, R., Ogozalek, K.L., Durkin, M.M., Lakhlani, P.P., Bonini, J.A., Pathirana, S., Boyle, N., Pu, X., Koura-nova, E., Lichtblau, H., Ochoa, F.Y., Branchek, T.A., Gerald, C. Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc. Natl. Acad. Sci. USA 2001, 98:8966-8971.

Xu, Y., Zhu, K., Hong, G., Wu, W., Baudhuin, L.M., Xiao, Y., Damron, D.S. Sphin-gosylphosphorylcholine is a ligand for ovarian cancer G-protein-coupled receptor 1. Nat. Cell Biol. 2000, 5:261-267.

Hancock, A.A., Esbenshade, T.A., Krueger, K.M., Yao, B.B. Genetic and pharmacological aspects of histamine H3 receptor heterogeneity. Life Sci. 2003, 73:3043-3072. Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., Shimizu, T. A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 1997, 387:620-624. Johnson, J.A. and Lima, J.J. Drug receptor/effector polymorphisms and pharmacogenetics: current status and challenges. Pharmacogenetics 2003, 13:525-534. Sadee, W. Hoeg, E., Lucas, J., Wang, D. Genetic variations in human G proteincoupled receptors: implications for drug therapy. AAPS PharmSci. 2001, 3:1-26. Seifert, R. and Wenzel-Seifert, K. Constitutive activity of G protein-coupled receptors: cause of disease and common property of wild-type receptors. Naunyn-Schmiede-berg's Arch. Pharmacol. 2002, 366:381-416.

Rosenthal, W., Seibold, A., Antaramian, A., Lonergan, M., Arthus, M.F., Hendy, G.N., Birnbaumer, M., Bichet, D.G. Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature 1992, 359:233-235. Barak, L.S., Oakley, R.H., Laporte, S.A., Caron, M.G. Constitutive arrestin-mediated desensitization of a human vasopression receptor mutant associated with nephrogenic diabetes insipidus. Proc. Natl. Acad. Sci. USA 2001, 98:93-98. Turki, J., Pak, J., Green, S.A., Martin, R.J., Liggett, S.B. Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma: evidence that Gly16 correlates with the nocturnal phenotype. J. Clin. Invest. 1995, 95:1635-1641. Mitchell, B.D., Blangero, J., Comuzzie, A.G., Almasy, L.A., Shuldiner, A.R., Silver, K., Stern, M.P., MacCluer, J.W., Hixson, J.E. A paired sibling analysis of the b3-adrenergic receptor and obesity in Mexican Americans. J. Clin. Invest. 1998, 101:584-587.

Hirata, T., Kakizuka, A., Ushikubi, F., Fuse, I., Okuma, M., Narumiya, S. Arg 60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. J. Clin. Invest. 1994, 94:1662-1667.

Hollopeter, G., Jantzen, H.M., Vincent, D., Li, G., England, L., Ramakrishnan, V., Yang, R.B., Nurden, P, Nurden, A., Julius, D., Conley, P.B. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001, 409:202-207. Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, PJ., Nishino, S., Mignot, E. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 1999, 98:365-376. Karasinska, J.M., George, S.R., O'Dowd, B.F. Family 1 G protein-coupled receptor function in the CNS: insights from gene knockout mice. Brain Res. Rev. 2003, 41:125-152.

Zambrowicz, B.P and Sands, A.T. Knockouts model the 100 best-selling drugs: will they model the next 100? Nat. Rev. Drug Disc. 2003, 2:38-51.

Zambrowicz, B.P., Turner, C.A., Sands, A.T. Predicting drug efficacy: knockouts model pipeline drugs of the pharmaceutical industry. Curr. Opin. Pharmacol. 2003,


43. Van Oekelen, D., Luyten, W.H.M.L., Leysen, J.E. Ten years of antisense inhibition of brain G protein-coupled receptor function. Brain Res. Rev. 2003, 42:123-142.

44. Dorsett, Y. and Tuschl, T. siRNAs: applications in functional genomics and potential as therapeutics. Nat. Rev. Drug Disc. 2004, 3:318-328.

45. Jain, K.K. RNAi and siRNA in target validation. Drug Disc. Today 2004, 9:307-309.

46. Sioud, M. Therapeutic siRNAs. Trends Pharmacol. Sci. 2004, 25:22-28.

47. Martinez, M.A., Gutierrez, A., Armand-Ugon, M., Blanco, J., Parera, M., Gomez, J., Clotet, B., Este, J.A. Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication. AIDS 2002, 16:2385-2390.

48. Radu, C.G., Yang, L.V., Riedinger, M., Au, M., Witte, O.N. T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proc. Natl. Acad. Sci. USA 2004, 101:245-250.

49. Bissantz, C., Bernard, P, Hibert, M., Rognan, D. Protein-based virtual screening of chemical databases. II. Are homology models of G protein-coupled receptors suitable targets? Proteins 2003, 50:5-25.

50. Bleicher, K.H., Green, L.G., Martin, R.E., Rogers-Evans, M. Ligand identification for G-protein-coupled receptors: a lead generation perspective. Curr. Opin. Chem. Biol. 2004, 8:287-296.

51. Palczewski, K., Kumasaka, T., Hori, T., Behnke, C.A., Motoshima, H., Fox, B.A., Le Trong, I., Teller, D.C., Okada, T., Stenkamp, R.E., Yamamoto, M., Miyano, M. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 2000, 289:739-745.

52. Varady, J., Wu, X., Fang, X., Min, J., Hu, Z., Levant, B., Wang, S. Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor: discovery of novel and potent D3 ligands through a hybrid pharmacophore- and structure-based database searching approach. J. Med. Chem. 2003, 46:4377-4392.

53. Evers, A. and Klebe, G. Ligand-supported homology modeling of G-protein-coupled receptor sites: models sufficient for successful virtual screening. Angew Chem. Int. Ed. Engl. 2004, 43:248-251.

54. Rohrer, S.P., Birzin, E.T., Mosley, R.T., Berk, S.C., Hutchins, S.M., Shen, D.M., Xiong, Y., Hayes, E.C., Parmar, R.M., Foor, F., Mitra, S.W., Degrado, S.J., Shu, M., Klopp, J.M., Cai, S.J., Blake, A., Chan, W.W., Pasternak, A., Yang, L., Patchett, A.A., Smith, R.G., Chapman, K.T., Schaeffer, J.M. Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science 1998, 282:737-740.

55. Hardy, L.W. and Peet, N.P. The multiple orthogonal tools approach to define molecular causation in the validation of druggable targets. Drug Disc. Today 2004, 9:117-126.

56. Evans, B.E., Rittle, K.E., Bock, M.G., DiPardo, R.M., Freidinger, R.M., Whitter, W.L., Lundell, G.F., Veber, D.F., Anderson, P.S., Chang, R.S, Lotti, V.J., Cerino, D.J., Chen, T.B., Kling, PJ., Kunkel, K.A., Springer, J.P., Hirshfield, J. Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists. J. Med. Chem. 1988, 31:2235-2246.

57. Klabunde, T. and Hessler, G. Drug design strategies for targeting G protein-coupled receptors. Chem. Bio. Chem. 2002, 3:928-944.

58. Bleicher, K.H., Green, L.G., Martin, R.E., Rogers-Evans, M. Ligand identification for G-protein-coupled receptors: a lead generation perspective. Curr. Opin. Chem. Biol. 2004, 8:287-296.

59. Guo, T. and Hobbs, D.W. Privileged structure-based combinatorial libraries targeting G protein-coupled receptors. Assay Drug Dev. Tech. 2003, 1:579-592.

60. Bondensgaard, K., Ankersen, M., Thogersen, H., Hansen, B.S., Wulff, B.S., Bywater, R.P. Recognition of privileged structures by G protein-coupled receptors. J. Med. Chem. 2004, 47: 888-899.

61. Morisset, S., Rouleau, A., Ligneau, X., Gbahou, F., Tardivel-Lacombe, J., Stark, H., Schunack, W., Ganellin, C.R., Schwartz, J.C., Arrang, J.M. High constitutive activity of native H3 receptors regulates histamine neurons in brain. Nature 2000, 408:860-864.

62. Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Delivery Rev. 2001, 46:3-26.

63. Fernandez, D., Ghanta, A., Kauffman, G.W., Sanguinetti, M.C. Physicochemical features of the HERG channel drug binding site. J. Biol. Chem. 2004, 279:10120-10127.

64. Kamohara, M., Takasaki, J., Matsumoto, M., Saito, T., Ohishi, T., Ishii, H., Furuichi, K. Molecular cloning and characterization of another leukotriene B4 receptor. J. Biol. Chem. 2000, 275:27000-27004.

65. Civelli, O., Nothacker, H.P., Saito, Y., Wang, Z. Lin, S.H., Reinscheid, R.K. Novel neurotransmitters as natural ligands of orphan G protein-coupled receptors. Trends Neurosci. 2001, 24:230-237.

66. Meunier, J.C., Mollereau, C., Toll, L., Suaudeau, C., Moisand, C., Alvinerie, P, Butour, J., Guillemot, J.C., Ferrara, P., Monsarrat, B., Mazarguil, H., Vassart, G., Parmentier, M., Costentin, J. Isolation and structure of the endogenous agonist of opioid receptor like ORL1 receptor. Nature 1995, 377:532-535.

67. Wise, A., Jupe, S.C., Rees, S. The identification of ligands at orphan G proteincoupled receptors Annu. Rev. Pharmacol. Toxicol. 2004, 44:43-66.

68. Jones, K.A., Borowsky, B. Tamm, J.A., Craig, D.A., Durkin, M.M., Dai, M., Yao, W.J., Johnson, M., Gunwaldsen, C., Huang, L.Y., Tang, C., Shen, Q., Salon, J.A., Morse, K., Laz, T., Smith, K.E., Nagarathnam, D., Noble, S.A., Branchek, T.A., Gerald, C. GABAB receptors function as a heteromeric assembly of the subunits of GABABR1 and GABABR2. Nature 1998, 396:674-679.

69. White, J.H., Wise, A., Main, M.J., Green, A., Fraser, N.J., Disney, G.H., Barnes, A.A., Emson, P., Foord, S.M., Marshall, F.H. Heterodimerization is required for the formation of a functional GABAB receptor. Nature 1998, 396:679-682.

70. Kaupmann, K., Malitschek, B., Schuler, V., Heid, J., Froestl, W., Beck, P, Mosbacher, J., Bischoff, S., Kulik, A., Shigemoto, R., Karschin, A., Bettler, B. GABAB-receptor subtypes assemble into functional heteromeric complexes. Nature 1998, 396:683-687.

71. Tallman, J. Dimerization of G-protein-coupled receptors: implications for drug design and signaling. Neuropsychopharmacology 2000, 23:S1-S2.

72. Milligan, G. G protein-coupled receptor dimerization: function and ligand pharmacology. Mol. Pharmacol. 2004, 66:1-7

73. George, S.R., O'Dowd, B.F., Lee, S.P G protein-coupled receptor oligomerization and its potential for drug discovery. Nat. Rev. Drug Disc. 2002, 1:808-819.

4 G Protein-Coupled Receptors as Cardiovascular Drug Targets

Delicious Diabetic Recipes

Delicious Diabetic Recipes

This brilliant guide will teach you how to cook all those delicious recipes for people who have diabetes.

Get My Free Ebook

Post a comment