Structures of G protein-coupled receptors reveal new opportunities for drug discovery

Drug Discovery Today

Volumn 20, Issue 11, 2015, Pages 1355-1364

  Cooke, Robert M ^a   Brown, Alastair J H ^a   Marshall, Fiona H ^a   Mason, Jonathan S ^a  

^a Heptares Therapeutics Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; LIGAND; PROTEIN BINDING;

DRUG DEVELOPMENT; LIGAND BINDING; LIPOPHILICITY; MEDICAL INFORMATION; MOLECULAR DYNAMICS; PROTEIN BINDING; PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; BINDING SITE; CHEMISTRY; DRUG DESIGN; HUMAN; METABOLISM; PROCEDURES;

BINDING SITES; DRUG DESIGN; DRUG DISCOVERY; HUMANS; LIGANDS; PROTEIN BINDING; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84947032095     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2015.08.003     Document Type: Review

References (58)

1. J.P. Overington, and et al. How many drug targets are there? Nat Rev. Drug Discov. 5 2006 993 996
2. K. Pawlczewski, and et al. Crystal structure of rhodopsin: a G protein-coupled receptor Science 289 2000 739 745
3. M.J. Serrano-Vega, and et al. Conformational thermostabilization of the beta1-adrenergic receptor in a detergent-resistant form Proc. Natl. Acad. Sci. U. S. A. 105 2008 877 882
4. V. Cherezov, and et al. High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor Science 318 2007 1258 1265
5. T. Warne, and et al. Structure of a β1-adrenergic G-protein coupled receptor Nature 454 2008 486 491
6. V.-P. Jaakola, and et al. The 2.6 Angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist Science 322 2008 1211 1217
7. K. Hollenstein, and et al. Structure of class B GPCR corticotropin-releasing factor receptor 1 Nature 499 2013 438 443
8. F.Y. Siu, and et al. Structure of the human glucagon class B G-protein-coupled receptor Nature 499 2013 444 449
9. H. Wu, and et al. Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator Science 344 2014 58 64
10. A.S. Doré, and et al. Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain Nature 511 2014 557 562
11. C. Wang, and et al. Structure of the human smoothened receptor bound to an antitumour agent Nature 497 2013 338 343
12. S.G. Rasmussen, and et al. Structure of a nanobody-stabilised active state of the β(2) adrenoreceptor Nature 469 2011 175 180
13. G. Lebon, and et al. Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation Nature 474 2011 521 525
14. T. Warne, and et al. The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor Nature 469 2011 241 244
15. S.G. Rasmussen, and et al. Crystal structure of the β2 adrenergic receptor-Gs protein complex Nature 477 2011 549 555
16. B.G. Tehan, and et al. Unifying family A GPCR theories of activation Pharmacol. Ther. 143 2014 51 60
17. J.F. White, and et al. Structure of the agonist-bound neurotensin receptor NTS1 Nature 490 2012 508 513
18. A. Srivastava, and et al. High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875 Nature 513 2014 124 127
19. Q. Tan, and et al. Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex Science 341 2013 1387 1390
20. C. Zhang, and et al. High-resolution crystal structure of human protease-activated receptor 1 Nature 492 2012 387 392
21. J. Yin, and et al. Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant Nature 519 2015 247 250
22. A.J. Venkatakrishnan, and et al. Molecular signatures of G-protein-coupled receptors Nature 494 2013 185 194
23. B. Wu, and et al. Structures of the cxcr4 chemokine GPCR with small-molecule and cyclic peptide antagonists Science 330 2010 1066 1071
24. 12 receptor in complex with an antithrombotic drug Nature 509 2014 115 118
25. G. Ruiz-Gómez, and et al. Over one hundred peptide-activated G protein-coupled receptors recognize ligands with turn structure Chem. Rev. 110 2010 PR1 PR41
26. C.S. Tautermann, and et al. What can we learn from molecular dynamics simulations for GPCR drug design? Comp Struct. Biotech. J. 13 2015 111 121
27. R.O. Dror, and et al. Pathway and mechanism of drug binding to G-protein-coupled receptors Proc. Natl. Acad. Sci. U. S. A. 108 2011 13118 13123
28. A.C. Kruse, and et al. Activation and allosteric modulation of a muscarinic acetylcholine receptor Nature 504 2013 101 106
29. M.A. Hanson, and et al. Crystal structure of a lipid G protein-coupled receptor Science 335 2012 851 855
30. G.P. Anderson, and et al. Why are long-acting beta-adrenoceptor agonists long-acting? Eur. Resp. J. 7 1994 569 578
31. 1 receptor Nature 520 2015 317 321
32. 1 receptors in vitro and in vivo Brit. J. Pharm. 164 2011 992 1007
33. K. Bennett, and et al. Structures of mGluRs shed light on the challenges of drug development of allosteric modulators Curr. Opin. Pharmacol. 20 2015 1 7
34. I. Kufareva, and et al. Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: meeting new challenges Structure 22 2014 1120 1139
35. P. Keov, and et al. Molecular mechanisms of bitopic ligand engagement with the M1 muscarinic acetylcholine receptor J. Biol. Chem. 289 2014 23817 23837
36. W.M. Nolte, and et al. A potentiator of orthosteric ligand activity at GLP-1R acts via covalent modification Nat. Chem. Biol. 10 2014 629 631
37. G. Andrews, and et al. An intracellular allosteric site for a specific class of antagonists of the CC chemokine G protein-coupled receptors CCR4 and CCR5 Mol. Pharmacol. 73 2008 855 867
38. C. Wang, and et al. Structural basis for molecular recognition at serotonin receptors Science 340 2013 610 614
39. M. Congreve, and et al. Structure-based drug design for G protein-coupled receptors Prog. Med. Chem. 53 2014 1 63
40. M. Congreve, and et al. Progress in structure based drug design for G protein-coupled receptors J. Med. Chem. 54 2011 4283 4311
41. J.S. Mason, and et al. New insights from structural biology into the druggability of G protein-coupled receptors Trends Pharmacol. Sci. 33 2012 249 260
42. J.S. Mason, and et al. High end GPCR design: crafted ligand design and druggability analysis using protein structure, lipophilic hotspots and explicit water networks In Silico Pharmacol. 1 2013 23
43. P.J. Goodford A computational procedure for determining energetically favorable binding sites on biologically important macromolecules J. Med. Chem. 28 1985 849 857
44. Molecular Discovery GRID/FLAP/WaterFLAP (2013). Available at: http://www.moldiscovery.com/
45. Schrödinger L. WaterMap. Available at: http://www.schrodinger.com/
46. C.J. Langmead, and et al. Identification of novel adenosine A2A receptor antagonists by virtual screening J. Med. Chem. 55 2012 1904 1909
47. G. McGaughey, and et al. Shaping suvorexant: application of experimental and theoretical methods for driving synthetic designs J. Comput. Aided Mol. Des. 28 2014 5 12
48. W. Liu, and et al. Structural basis for allosteric regulation of GPCRs by sodium ions Science 337 2012 232 236
49. S.P. Andrews, and et al. Structure-based drug design of chromone antagonists of the adenosine A2A receptor Med. Chem. Comm. 5 2014 571 575
50. A. Bortolato, and et al. Water network perturbation in ligand binding: adenosine A2A antagonists as a case study J. Chem. Inf. Model. 53 2013 1700 1713
51. D. Sabbadin, and et al. Supervised molecular dynamics (SuMD) as a helpful tool to depict GPCR-ligand recognition pathway in a nanosecond timescale J. Chem. Inf. Model. 54 2014 372 376
52. A.S. Doré, and et al. Structure of the adenosine A2A receptor in complex with ZM241385 and the xanthines XAC and caffeine Structure 19 2011 1283 1293
53. 2A antagonists using structure based drug design J. Med. Chem. 55 2012 1898 1903
54. J. Zhang, and et al. Agonist-bound structure of the human P2Y12 receptor Nature 509 2014 119 122
55. M.M. Hann Molecular obesity, potency and other addictions in drug discovery Med. Chem. Commun. 2 2011 349 355
56. A.A. Alex, and D.S. Millan Contribution of structure-based drug design to the discovery of marketed drugs D.J. Livingstone, A.M. Davis, Drug Design Strategies 2012 Springer 108 163
57. M. Hauge, and et al. GPR40 (FFAR1) - combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo Mol. Metab. 4 2014 3 14
58. 2 receptor J. Med. Chem. 58 2015 2703 2717