Pharmacological characterization of a small-molecule agonist for the chemokine receptor CXCR3

British Journal of Pharmacology

Volumn 166, Issue 3, 2012, Pages 898-911

  Scholten, D J ^a   Canals, M ^a   Wijtmans, M ^a   De Munnik, S ^a   Nguyen, P ^a   Verzijl, D ^a   De Esch, I J P ^a   Vischer, H F ^a   Smit, M J ^a   Leurs, R ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

Author keywords

arrestin; allosteric; BRET; CXCR3; ligand biased signalling; small molecule agonist; VUF10661

Indexed keywords

ADENYLATE CYCLASE; BETA ARRESTIN 1; BETA ARRESTIN 2; CHEMOKINE RECEPTOR AGONIST; CHEMOKINE RECEPTOR CXCR3; CHEMOKINE RECEPTOR CXCR4; COMPLEMENTARY DNA; CXCL11 CHEMOKINE; CXCL9 CHEMOKINE; CYCLIC AMP; G PROTEIN COUPLED RECEPTOR KINASE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; UNCLASSIFIED DRUG; VUF 10661;

ALLOSTERISM; ANIMAL CELL; ARTICLE; BINDING ASSAY; BINDING SITE; BIOSENSOR; CHEMOTAXIS; CONTROLLED STUDY; DOSE RESPONSE; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; HUMAN CELL; INTERNALIZATION; LIGAND BINDING; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION;

ALLOSTERIC REGULATION; ANIMALS; CELL CULTURE TECHNIQUES; CELL MEMBRANE; CHEMOKINE CXCL10; CHEMOKINE CXCL11; CHEMOTAXIS; CYCLIC AMP; DNA, COMPLEMENTARY; DOSE-RESPONSE RELATIONSHIP, DRUG; HEK293 CELLS; HUMANS; ISOQUINOLINES; LIGANDS; MICE; PRECURSOR CELLS, B-LYMPHOID; PROTEIN BINDING; RADIOLIGAND ASSAY; RECEPTORS, CELL SURFACE; RECEPTORS, CXCR3; SMALL MOLECULE LIBRARIES; TRANSFECTION;

EID: 84860855040     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01648.x     Document Type: Article

References (57)

1. Alexander SPH, Mathie A, Peters JA, (2011). Guide to Receptors and Channels (GRAC), 5th Edition. Br J Pharmacol 164 (Suppl. 1): S1-S324.
2. Allen S, Crown S, Handel T, (2007). Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 25: 787-820.
3. Barak L, Salahpour A, Zhang X, Masri B, Sotnikova T, Ramsey A, et al,. (2008). Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor. Mol Pharmacol 74: 585-594.
4. Bauer J, Baechler E, Petri M, Batliwalla F, Crawford D, Ortmann W, et al,. (2006). Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus. PLoS Med 3: e491.
5. Blanpain C, Doranz BJ, Bondue A, Govaerts C, De Leener A, Vassart G, et al,. (2003). The core domain of chemokines binds CCR5 extracellular domains while their amino terminus interacts with the transmembrane helix bundle. J Biol Chem 278: 5179-5187.
6. Bonacchi A, Romagnani P, Romanelli RG, Efsen E, Annunziato F, Lasagni L, et al,. (2001). Signal transduction by the chemokine receptor CXCR3: activation of Ras/ERK, Src, and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes. J Biol Chem 276: 9945-9954.
7. Casarosa P, Menge WM, Minisini R, Otto C, van Heteren J, Jongejan A, et al,. (2003). Identification of the first nonpeptidergic inverse agonist for a constitutively active viral-encoded G protein-coupled receptor. J Biol Chem 278: 5172-5178.
8. Cheng Y-C, Prusoff W, (1973). Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50% inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22: 3099-3108.
9. Cole K, Strick C, Paradis T, Ogborne K, Loetscher M, Gladue R, et al,. (1998). Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med 187: 2009-2021.
10. Colvin RA, Campanella GSV, Sun J, Luster AD, (2004). Intracellular domains of CXCR3 that mediate CXCL9, CXCL10, and CXCL11 function. J Biol Chem 279: 30219-30227.
11. Cox M, Jenh C, Gonsiorek W, Fine J, Narula S, Zavodny P, et al,. (2001). Human interferon-inducible 10-kDa protein and human interferon-inducible T cell alpha chemoattractant are allotopic ligands for human CXCR3: differential binding to receptor states. Mol Pharmacol 59: 707-715.
12. Dagan-Berger M, Feniger-Barish R, Avniel S, Wald H, Galun E, Grabovsky V, et al,. (2006). Role of CXCR3 carboxyl terminus and third intracellular loop in receptor-mediated migration, adhesion and internalization in response to CXCL11. Blood 107: 3821-3831.
13. DeWire S, Ahn S, Lefkowitz R, Shenoy S, (2007). Beta-arrestins and cell signaling. Annu Rev Physiol 69: 483-510.
14. Enghard P, Humrich J, Rudolph B, Rosenberger S, Biesen R, Kuhn A, et al,. (2009). CXCR3+CD4+ T cells are enriched in inflamed kidneys and urine and provide a new biomarker for acute nephritis flares in systemic lupus erythematosus patients. Arthritis Rheum 60: 199-206.
15. Ferguson SS, Downey WE 3rd, Colapietro AM, Barak LS, Menard L, Caron MG, (1996). Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 271: 363-366.
16. Fong AM, Premont RT, Richardson RM, Yu YR, Lefkowitz RJ, Patel DD, (2002). Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice. Proc Natl Acad Sci USA 99: 7478-7483.
17. Gao P, Zhou XY, Yashiro-Ohtani Y, Yang YF, Sugimoto N, Ono S, et al,. (2003). The unique target specificity of a nonpeptide chemokine receptor antagonist: selective blockade of two Th1 chemokine receptors CCR5 and CXCR3. J Leukoc Biol 73: 273-280.
18. Garcia-Perez J, Rueda P, Staropoli I, Kellenberger E, Alcami J, Arenzana-Seisdedos F, et al,. (2011). New insights into the mechanisms whereby low molecular weight CCR5 ligands inhibit HIV-1 infection. J Biol Chem 286: 4978-4990.
19. Hancock W, Lu B, Gao W, Csizmadia V, Faia K, King J, et al,. (2000). Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med 192: 1515-1520.
20. Harrison C, Traynor J, (2003). The [35S]GTPgammaS binding assay: approaches and applications in pharmacology. Life Sci 74: 489-508.
21. Jiang LI, Collins J, Davis R, Lin KM, DeCamp D, Roach T, et al,. (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.
22. Kao J, Kobashigawa J, Fishbein M, MacLellan W, Burdick M, Belperio J, et al,. (2003). Elevated serum levels of the CXCR3 chemokine ITAC are associated with the development of transplant coronary artery disease. Circulation 107: 1958-1961.
23. Kenakin T, Miller LJ, (2010). Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol Rev 62: 265-304.
24. Kofuku Y, Yoshiura C, Ueda T, Terasawa H, Hirai T, Tominaga S, et al,. (2009). Structural basis of the interaction between chemokine stromal cell-derived factor-1/CXCL12 and its G-protein-coupled receptor CXCR4. J Biol Chem 284: 35240-35250.
25. Kollias-Baker CA, Ruble J, Jacobson M, Harrison JK, Ozeck M, Shryock JC, et al,. (1997). Agonist-independent effect of an allosteric enhancer of the A1 adenosine receptor in CHO cells stably expressing the recombinant human A1 receptor. J Pharmacol Exp Ther 281: 761-768.
26. Kondru R, Zhang J, Ji C, Mirzadegan T, Rotstein D, Sankuratri S, et al,. (2008). Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists. Mol Pharmacol 73: 789-800.
27. de Kruijf P, van Heteren J, Lim H, Conti P, van der Lee M, Bosch L, et al,. (2009). Nonpeptidergic allosteric antagonists differentially bind to the CXCR2 chemokine receptor. J Pharmacol Exp Ther 329: 783-790.
28. Lanzafame A, Guida E, Christopoulos A, (2004). Effects of anandamide on the binding and signaling properties of M1 muscarinic acetylcholine receptors. Biochem Pharmacol 68: 2207-2219.
29. Lit L, Wong C, Tam L, Li E, Lam C, (2006). Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus. Ann Rheum Dis 65: 209-215.
30. Loetscher M, Gerber B, Loetscher P, Jones S, Piali L, Clark-Lewis I, et al,. (1996). Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med 184: 963-969.
31. Loetscher M, Loetscher P, Brass N, Meese E, Moser B, (1998). Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization. Eur J Immunol 28: 3696-3705.
32. Mach F, Sauty A, Iarossi AS, Sukhova GK, Neote K, Libby P, et al,. (1999). Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells. J Clin Invest 104: 1041-1050.
33. Masri B, Salahpour A, Didriksen M, Ghisi V, Beaulieu JM, Gainetdinov RR, et al,. (2008). Antagonism of dopamine D2 receptor/beta-arrestin 2 interaction is a common property of clinically effective antipsychotics. Proc Natl Acad Sci USA 105: 13656-13661.
34. Meiser A, Mueller A, Wise EL, McDonagh EM, Petit SJ, Saran N, et al,. (2008). The chemokine receptor CXCR3 is degraded following internalization and is replenished at the cell surface by de novo synthesis of receptor. J Immunol 180: 6713-6724.
35. Melter M, Exeni A, Reinders ME, Fang JC, McMahon G, Ganz P, et al,. (2001). Expression of the chemokine receptor CXCR3 and its ligand IP-10 during human cardiac allograft rejection. Circulation 104: 2558-2564.
36. Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG, (2001). Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis. J Biol Chem 276: 19452-19460.
37. Pierce KL, Lefkowitz RJ, (2001). Classical and new roles of beta-arrestins in the regulation of G-protein-coupled receptors. Nat Rev Neurosci 2: 727-733.
38. Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, et al,. (1998). The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 101: 746-754.
39. Ritter SL, Hall RA, (2009). Fine-tuning of GPCR activity by receptor-interacting proteins. Nat Rev Mol Cell Biol 10: 819-830.
40. Rosenkilde MM, Gerlach LO, Jakobsen JS, Skerlj RT, Bridger GJ, Schwartz TW, (2004). Molecular mechanism of AMD3100 antagonism in the CXCR4 receptor: transfer of binding site to the CXCR3 receptor. J Biol Chem 279: 3033-3041.
41. Saita Y, Kodama E, Orita M, Kondo M, Miyazaki T, Sudo K, et al,. (2006). Structural basis for the interaction of CCR5 with a small molecule, functionally selective CCR5 agonist. J Immunol 177: 3116-3122.
42. Sauty A, Colvin RA, Wagner L, Rochat S, Spertini F, Luster AD, (2001). CXCR3 internalization following T cell-endothelial cell contact: preferential role of IFN-inducible T cell {alpha} chemoattractant (CXCL11). J Immunol 167: 7084-7093.
43. Smit MJ, Verdijk P, van der Raaij-Helmer EM, Navis M, Hensbergen PJ, Leurs R, et al,. (2003). CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood 102: 1959-1965.
44. Sorensen TL, Tani M, Jensen J, Pierce V, Lucchinetti C, Folcik VA, et al,. (1999). Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 103: 807-815.
45. Stephenson RP, (1956). A modification of receptor theory. Br J Pharmacol 11: 379-393.
46. Storelli S, Verzijl D, Al-Badie J, Elders N, Bosch L, Timmerman H, et al,. (2007). Synthesis and structure-activity relationships of 3H-quinazolin-4-ones and 3H-pyrido[2,3-d]pyrimidin-4-ones as CXCR3 receptor antagonists. Arch Pharm (Weinheim) 340: 281-291.
47. Stroke I, Cole A, Simhadri S, Brescia M, Desai M, Zhang J, et al,. (2006). Identification of CXCR3 receptor agonists in combinatorial small-molecule libraries. Biochem Biophys Res Commun 349: 221-228.
48. Su Y, Raghuwanshi SK, Yu Y, Nanney LB, Richardson RM, Richmond A, (2005). Altered CXCR2 signaling in beta-arrestin-2-deficient mouse models. J Immunol 175: 5396-5402.
49. Thompson BD, Jin Y, Wu KH, Colvin RA, Luster AD, Birnbaumer L, et al,. (2007). Inhibition of G alpha i2 activation by G alpha i3 in CXCR3-mediated signaling. J Biol Chem 282: 9547-9555.
50. Urban J, Clarke W, von Zastrow M, Nichols D, Kobilka B, Weinstein H, et al,. (2007). Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther 320: 1-13.
51. Verzijl D, Storelli S, Scholten DJ, Bosch L, Reinhart TA, Streblow DN, et al,. (2008). Noncompetitive antagonism and inverse agonism as mechanism of action of nonpeptidergic antagonists at primate and rodent CXCR3 chemokine receptors. J Pharmacol Exp Ther 325: 544-555.
52. van Wanrooij EJ, de Jager SC, van Es T, de Vos P, Birch HL, Owen DA, et al,. (2008). CXCR3 antagonist NBI-74330 attenuates atherosclerotic plaque formation in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 28: 251-257.
53. Walser TC, Ma X, Kundu N, Dorsey R, Goloubeva O, Fulton AM, (2007). Immune-mediated modulation of breast cancer growth and metastasis by the chemokine Mig (CXCL9) in a murine model. J Immunother 30: 490-498.
54. Wijtmans M, Verzijl D, Leurs R, de Esch IJ, Smit MJ, (2008). Towards small-molecule CXCR3 ligands with clinical potential. ChemMedChem 3: 861-872.
55. Wise EL, Duchesnes C, da Fonseca PC, Allen RA, Williams TJ, Pease JE, (2007). Small molecule receptor agonists and antagonists of CCR3 provide insight into mechanisms of chemokine receptor activation. J Biol Chem 282: 27935-27943.
56. Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, et al,. (2010). Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330: 1066-1071.
57. Yates CC, Krishna P, Whaley D, Bodnar R, Turner T, Wells A, (2010). Lack of CXC chemokine receptor 3 signaling leads to hypertrophic and hypercellular scarring. Am J Pathol 176: 1743-1755.