Allosteric modulation of chemoattractant receptors

Frontiers in Immunology

Volumn 7, Issue MAY, 2016, Pages

  Allegretti, Marcello ^a   Cesta, Maria Candida ^a   Locati, Massimo ^b,c  

^a Chemistry Section   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

^c HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

Author keywords

Biased signaling; Chemoattractant; Chemokine receptor; Functional selectivity; Leukocyte recruitment

Indexed keywords

CHEMOATTRACTANT; CHEMOKINE RECEPTOR; CHEMOKINE RECEPTOR CXCR1; CHEMOKINE RECEPTOR CXCR2; CHEMOKINE RECEPTOR CXCR4; G PROTEIN COUPLED RECEPTOR; INTERLEUKIN 8; LADARIXIN; PLERIXAFOR; REPARIXIN; STROMAL CELL DERIVED FACTOR 1;

ALLOSTERISM; AUTOIMMUNITY; BINDING SITE; CELL MIGRATION; COMMON VARIABLE IMMUNODEFICIENCY; DRUG EFFICACY; DRUG RESEARCH; DRUG TARGETING; IMMUNOMODULATION; INFLAMMATION; LEUKOCYTE; MUTAGENESIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION;

EID: 84973569808     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2016.00170     Document Type: Review

References (65)

1. Lagerstrom MC, Schioth HB. Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat Rev Drug Discov (2008) 7:339-57. doi: 10.1038/nrd2518
2. Huang J, Chen K, Gong W, Dunlop NM, Wang JM. G-protein coupled chemoattractant receptors and cancer. Front Biosci (2008) 13:3352-63. doi:10.2741/2930
3. Oldham WM, Hamm HE. Structural basis of function in heterotrimeric G proteins. Q Rev Biophys (2006) 39:117-66. doi:10.1017/S0033583506004306
4. Rask-Andersen M, Almen MS, Schioth HB. Trends in the exploitation of novel drug targets. Nat Rev Drug Discov (2011) 10:579-90. doi:10.1038/nrd3478
5. Conn PJ, Lindsley CW, Meiler J, Niswender CM. Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat Rev Drug Discov (2014) 13:692-708. doi:10.1038/nrd4308
6. Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med (2006) 354:610-21. doi:10.1056/NEJMra052723
7. Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, et al. International Union of Basic and Clinical Pharmacology [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev (2014) 66:1-79. doi:10.1124/pr.113.007724
8. Bachelerie F, Graham GJ, Locati M, Mantovani A, Murphy PM, Nibbs R, et al. New nomenclature for atypical chemokine receptors. Nat Immunol (2014) 15:207-8. doi:10.1038/ni.2812
9. Kenakin T, Miller LJ. Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev (2010) 62:265-304. doi:10.1124/pr.108.000992
10. Gasparini F, Kuhn R, Pin JP. Allosteric modulators of group I metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives. Curr Opin Pharmacol (2002) 2:43-9. doi:10.1016/S1471-4892(01)00119-9
11. Knudsen LB, Kiel D, Teng M, Behrens C, Bhumralkar D, Kodra JT, et al. Small-molecule agonists for the glucagon-like peptide 1 receptor. Proc Natl Acad Sci U S A (2007) 104:937-42. doi:10.1073/pnas.0605701104
12. Kenakin T. Principles: receptor theory in pharmacology. Trends Pharmacol Sci (2004) 25:186-92. doi:10.1016/j.tips.2004.02.012
13. Perez DM, Karnik SS. Multiple signaling states of G-protein-coupled receptors. Pharmacol Rev (2005) 57:147-61. doi:10.1124/pr.57.2.2
14. Ding BS, Cao Z, Lis R, Nolan DJ, Guo P, Simons M, et al. Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis. Nature (2014) 505:97-102. doi:10.1038/nature12681
15. Poznansky MC, Olszak IT, Foxall R, Evans RH, Luster AD, Scadden DT. Active movement of T cells away from a chemokine. Nat Med (2000) 6:543-8. doi:10.1038/75022
16. Zlatopolskiy A, Laurence J. 'Reverse gear' cellular movement mediated by chemokines. Immunol Cell Biol (2001) 79:340-4. doi:10.1046/j.1440-1711.2001.01015.x
17. Bunting MD, Comerford I, McColl SR. Finding their niche: chemokines directing cell migration in the thymus. Immunol Cell Biol (2011) 89:185-96. doi:10.1038/icb.2010.142
18. Guyon A, Nahon JL. Multiple actions of the chemokine stromal cell-derived factor-1 alpha on neuronal activity. J Mol Endocrinol (2007) 38:365-76. doi:10.1677/JME-06-0013
19. Tan JHY, Ludeman JP, Wedderburn J, Canals M, Hall P, Butler SJ, et al. Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1). J Biol Chem (2013) 288:10024-34. doi:10.1074/jbc.M112.447359
20. Khoury E, Clement S, Laporte SA. Allosteric and biased G protein-coupled receptor signaling regulation: potentials for new therapeutics. Front Endocrinol (2014) 5:68. doi:10.3389/fendo.2014.00068
21. Luttrell LM, Kenakin TP. Refining efficacy: allosterism and bias in G protein-coupled receptor signaling. Methods Mol Biol (2011) 756:3-35. doi:10.1007/978-1-61779-160-4_1
22. Zweemer AJ, Toraskar J, Heitman LH, IJzerman AP. Bias in chemokine receptor signalling. Trends Immunol (2014) 35:243-52. doi:10.1016/j.it.2014.02.004
23. Changeux JP, Edelstein SJ. Allosteric mechanisms of signal transduction. Science (2005) 308:1424-8. doi:10.1126/science.1108595
24. Crump MP, Gong JH, Loetscher P, Rajarathnam K, Amara A, Arenzana-Seisdedos F, et al. Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1. EMBO J (1997) 16:6996-7007. doi:10.1093/emboj/16.23.6996
25. Tian Y, New DC, Yung LY, Allen RA, Slocombe PM, Twomey BM, et al. Differential chemokine activation of CC chemokine receptor 1-regulated pathways: ligand selective activation of Galpha 14-coupled pathways. Eur J Immunol (2004) 34:785-95. doi:10.1002/eji.200324166
26. Rajagopal S, Bassoni DL, Campbell JJ, Gerard NP, Gerard C, Wehrman TS. Biased agonism as a mechanism for differential signaling by chemokine receptors. J Biol Chem (2013) 288:35039-48. doi:10.1074/jbc.M113.479113
27. Kohout TA, Nicholas SL, Perry SJ, Reinhart G, Junger S, Struthers RS. Differential desensitization, receptor phosphorylation, beta-arrestin recruitment, and ERK1/2 activation by the two endogenous ligands for the CC chemokine receptor 7. J Biol Chem (2004) 279:23214-22. doi:10.1074/jbc.M402125200
28. Schmid CL, Bohn LM. Physiological and pharmacological implications of beta-arrestin regulation. Pharmacol Ther (2009) 121:285-93. doi:10.1016/j.pharmthera.2008.11.005
29. Berchiche YA, Gravel S, Pelletier ME, St-Onge G, Heveker N. Different effects of the different natural CC chemokine receptor 2b ligands on beta-arrestin recruitment, Galphai signaling, and receptor internalization. Mol Pharmacol (2011) 79:488-98. doi:10.1124/mol.110.068486
30. McCormick PJ, Segarra M, Gasperini P, Gulino AV, Tosato G. Impaired recruitment of Grk6 and beta-arrestin 2 causes delayed internalization and desensitization of a WHIM syndrome-associated CXCR4 mutant receptor. PLoS One (2009) 4:e8102. doi:10.1371/journal.pone.0008102
31. Zabel BA, Wang Y, Lewen S, Berahovich RD, Penfold ME, Zhang P, et al. Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-mediated tumor cell transendothelial migration by CXCR7 ligands. J Immunol (2009) 183:3204-11. doi:10.4049/jimmunol.0900269
32. Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, et al. Beta-arrestin-but not G protein-mediated signaling by the "decoy" receptor CXCR7. Proc Natl Acad Sci U S A (2010) 107:628-32. doi:10.1073/pnas.0912852107
33. Borroni EM, Cancellieri C, Vacchini A, Benureau Y, Lagane B, Bachelerie F, et al. β-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6. Sci Signal (2013) 6:S1-3. doi:10.1126/scisignal.2003627
34. Jensen PC, Thiele S, Ulven T, Schwartz TW, Rosenkilde MM. Positive versus negative modulation of different endogenous chemokines for CC-chemokine receptor 1 by small molecule agonists through allosteric versus orthosteric binding. J Biol Chem (2008) 283:23121-8. doi:10.1074/jbc.M803458200
35. Sachpatzidis A, Benton BK, Manfredi JP, Wang H, Hamilton A, Dohlman HG, et al. Identification of allosteric peptide agonists of CXCR4. J Biol Chem (2003) 278:896-907. doi:10.1074/jbc.M204667200
36. Quoyer J, Janz JM, Luo J, Ren Y, Armando S, Lukashova V, et al. Pepducin targeting the C-X-C chemokine receptor type 4 acts as a biased agonist favoring activation of the inhibitory G protein. Proc Natl Acad Sci U S A (2013) 110:E5088-97. doi:10.1073/pnas.1312515110
37. van der Westhuizen ET, Valant C, Sexton PM, Christopoulos A. Endogenous allosteric modulators of G protein-coupled receptors. J Pharmacol Exp Ther (2015) 353:246-60. doi:10.1124/jpet.114.221606
38. Allegretti M, Bertini R, Bizzarri C, Beccari A, Mantovani A, Locati M. Allosteric inhibitors of chemoattractant receptors: opportunities and pitfalls. Trends Pharmacol Sci (2008) 29:280-6. doi:10.1016/j.tips.2008.03.005
39. Melancon BJ, Tarr JC, Panarese JD, Wood MR, Lindsley CW. Allosteric modulation of the M1 muscarinic acetylcholine receptor: improving cognition and a potential treatment for schizophrenia and Alzheimer's disease. Drug Discov Today (2013) 18:1185-99. doi:10.1016/j.drudis.2013.09.005
40. Menniti FS, Lindsley CW, Conn PJ, Pandit J, Zagouras P, Volkmann RA. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks. Curr Top Med Chem (2013) 13:26-54. doi:10.2174/1568026611313010005
41. Moriconi A, Cesta MC, Cervellera MN, Aramini A, Coniglio S, Colagioia S, et al. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem (2007) 50:3984-4002. doi:10.1021/jm061469t
42. Christopoulos A. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov (2002) 1:198-210. doi:10.1038/nrd746
43. Mohr K, Schmitz J, Schrage R, Trankle C, Holzgrabe U. Molecular alliance-from orthosteric and allosteric ligands to dualsteric/bitopic agonists at G protein coupled receptors. Angew Chem Int Ed Engl (2013) 52:508-16. doi:10.1002/anie.201205315
44. Burford NT, Watson J, Bertekap R, Alt A. Strategies for the identification of allosteric modulators of G-protein-coupled receptors. Biochem Pharmacol (2011) 81:691-702. doi:10.1016/j.bcp.2010.12.012
45. Burford NT, Clark MJ, Wehrman TS, Gerritz SW, Banks M, O'Connell J, et al. Discovery of positive allosteric modulators and silent allosteric modulators of the mu-opioid receptor. Proc Natl Acad Sci U S A (2013) 110:10830-5. doi:10.1073/pnas.1300393110
46. Bizzarri C, Beccari AR, Bertini R, Cavicchia MR, Giorgini S, Allegretti M. ELR+ CXC chemokines and their receptors (CXC chemokine receptor 1 and CXC chemokine receptor 2) as new therapeutic targets. Pharmacol Ther (2006) 112:139-49. doi:10.1016/j.pharmthera.2006.04.002
47. Baggiolini M, Loetscher P. Chemokines in inflammation and immunity. Immunol Today (2000) 21:418-20. doi:10.1016/S0167-5699(00)01672-8
48. Tani K, Su SB, Utsunomiya I, Oppenheim JJ, Wang JM. Interferon-gamma maintains the binding and functional capacity of receptors for IL-8 on cultured human T cells. Eur J Immunol (1998) 28:502-7. doi:10.1002/(SICI)1521-4141(199802)28:02<502::AID-IMMU502>3.0.CO;2-5
49. Robertson MJ. Role of chemokines in the biology of natural killer cells. J Leukoc Biol (2002) 71:173-83
50. Russo RC, Garcia CC, Teixeira MM. Anti-inflammatory drug development: broad or specific chemokine receptor antagonists? Curr Opin Drug Discov Dev (2010) 13:414-27
51. Russo RC, Guabiraba R, Garcia CC, Barcelos LS, Roffe E, Souza AL, et al. Role of the chemokine receptor CXCR2 in bleomycin-induced pulmonary inflammation and fibrosis. Am J Respir Cell Mol Biol (2009) 40:410-21. doi:10.1165/rcmb.2007-0364OC
52. Bizzarri C, Allegretti M, Di Bitondo R, Cervellera MN, Colotta F, Bertini R. Pharmacological inhibition of Interleukin-8 (CXCL8) as a new approach for the prevention and treatment of several human diseases. Curr Med Chem Anti Inflamm Anti Allergy Agents (2003) 2:67-79. doi:10.2174/1568014033355844
53. Brandolini L, Allegretti M, Colagioia S, Novellini R, Colotta F, Bertini R, et al. Update on current and future pharmacological therapy of COPD. Curr Med Chem Anti Inflamm Anti Allergy Agents (2004) 3:81-101. doi:10.2174/1568014043355429
54. Bertini R, Allegretti M, Bizzarri C, Moriconi A, Locati M, Zampella G, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A (2004) 101:11791-6. doi:10.1073/pnas.0402090101
55. Souza DG, Bertini R, Vieira AT, Cunha FQ, Poole S, Allegretti M, et al. Repertaxin, a novel inhibitor of rat CXCR2 function, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury. Br J Pharmacol (2004) 143:132-42. doi:10.1038/sj.bjp.0705862
56. Garau A, Bertini R, Colotta F, Casilli F, Bigini P, Cagnotto A, et al. Neuroprotection with the CXCL8 inhibitor repertaxin in transient brain ischemia. Cytokine (2005) 30:125-31. doi:10.1016/j.cyto.2004.12.014
57. Cugini D, Azzollini N, Gagliardini E, Cassis P, Bertini R, Colotta F, et al. Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion. Kidney Int (2005) 67:1753-61. doi:10.1111/j.1523-1755.2005.00272.x
58. Citro A, Valle A, Cantarelli E, Mercalli A, Pellegrini S, Liberati D, et al. CXCR1/2 inhibition blocks and reverses type 1 diabetes in mice. Diabetes (2015) 64:1329-40. doi:10.2337/db14-0443
59. Larghi EL, Kaufman TS. Modulators of complement activation: a patent review (2008-2013). Expert Opin Ther Pat (2014) 24:665-86. doi:10.1517/13543776.2014.898063
60. Woodruff TM, Nandakumar KS, Tedesco F. Inhibiting the C5-C5a receptor axis. Mol Immunol (2011) 48:1631-42. doi:10.1016/j.molimm.2011.04.014
61. Moriconi A, Cunha TM, Souza GR, Lopes AH, Cunha FQ, Carneiro VL, et al. Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief. Proc Natl Acad Sci U S A (2014) 111:18799-18799. doi:10.1073/pnas.1417365111
62. Brogi S, Tafi A, Desaubry L, Nebigil CG. Discovery of GPCR ligands for probing signal transduction pathways. Front Pharmacol (2014) 5:255. doi:10.3389/fphar.2014.00255
63. Anderson CA, Solari R, Pease JE. Biased agonism at chemokine receptors: obstacles or opportunities for drug discovery? J Leukoc Biol (2015). doi:10.1189/jlb.2MR0815-392R
64. Rodriguez AL, Nong Y, Sekaran NK, Alagille D, Tamagnan GD, Conn PJ.A close structural analog of 2-methyl-6-(phenylethynyl)-pyridine acts as a neutral allosteric site ligand on metabotropic glutamate receptor subtype 5 and blocks the effects of multiple allosteric modulators. Mol Pharmacol (2005) 68:1793-802. doi:10.1124/mol.105.016139
65. Conn PJ, Christopoulos A, Lindsley CW. Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat Rev Drug Discov (2009) 8:41-54. doi:10.1038/nrd2760