Characterization of the molecular pharmacology of AMD3100: A specific antagonist of the G-protein coupled chemokine receptor, CXCR4

Biochemical Pharmacology

Volumn 72, Issue 5, 2006, Pages 588-596

  Fricker, Simon P ^a   Anastassov, Virginia ^a   Cox, Jennifer ^a   Darkes, Marilyn C ^a   Grujic, Ognjen ^a   Idzan, Stefan R ^a   Labrecque, Jean ^a   Lau, Gloria ^a   Mosi, Renee M ^a   Nelson, Kim L ^a   Qin, Ling ^a   Santucci, Zeffy ^a   Wong, Rebecca S Y ^a  

^a GENZYME CORPORATION   (United States)

Author keywords

AMD3100; Antagonist; Chemokine; CXCR4; G protein coupled receptor; Stromal cell derived factor

Indexed keywords

1,1' [1,4 PHENYLENEBIS(METHYLENE)]BIS(1,4,8,11 TETRAAZACYCLOTETRADECANE); CALCIUM; CHEMOKINE RECEPTOR CCR1; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR4; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR3; CHEMOKINE RECEPTOR CXCR4; CHEMOKINE RECEPTOR CXCR4 ANTAGONIST; G PROTEIN COUPLED RECEPTOR; GUANOSINE TRIPHOSPHATE; STROMAL CELL DERIVED FACTOR 1;

ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; ARTICLE; CALCIUM CELL LEVEL; CALCIUM TRANSPORT; CANCER CELL CULTURE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG BINDING SITE; DRUG INHIBITION; DRUG RECEPTOR BINDING; DRUG STRUCTURE; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; LIGAND BINDING; NEUTROPHIL CHEMOTAXIS; PRIORITY JOURNAL; STEM CELL MOBILIZATION; STRUCTURE ANALYSIS;

CALCIUM; CELL LINE; CHEMOKINES, CXC; CHEMOTAXIS; HETEROCYCLIC COMPOUNDS; HUMANS; PROTEIN BINDING; RECEPTORS, CXCR4; SIGNAL TRANSDUCTION;

EID: 33746685587     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2006.05.010     Document Type: Article

References (51)

1. Bleul C.C., Fuhlbrigge R.C., Casasnovas J.M., Aiuti A., and Springer T.A. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 184 (1996) 1101-1109
2. Baggiolini M. Chemokines and leukocyte traffic. Nature 392 (1998) 565-568
3. Nagasawa T., Tachibana K., and Kishimoto T. A novel CXC chemokine PBSF/SDF-1 and its receptor CXCR4: their functions in development, hematopoiesis and HIV infection. Semin Immunol 10 (1998) 179-185
4. Nagasawa T., Hirota S., Tachibana K., Takakura N., Nishikawa S., Kitamura Y., et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382 (1996) 635-638
5. Ma Q., Jones D., Borghesani P.R., Segal R.A., Nagasawa T., Kishimoto T., et al. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA 95 (1998) 9448-9453
6. Tachibana K., Hirota S., Iizasa H., Yoshida H., Kawabata K., Kataoka Y., et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 393 (1998) 591-594
7. Zou Y.R., Kottmann A.H., Kuroda M., Taniuchi I., and Littman D.R. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393 (1998) 595-599
8. Peled A., Petit I., Kollet O., Magid M., Ponomaryov T., Byk T., et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283 (1999) 845-848
9. + progenitors to peripheral blood. J Exp Med 185 (1997) 111-120
10. Feng Y., Broder C.C., Kennedy P.E., and Berger E.A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272 (1996) 872-877
11. Bleul C.C., Farzan M., Choe H., Parolin C., Clark-Lewis I., Sodroski J., et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 382 (1996) 829-833
12. Oberlin E., Amara A., Bachelerie F., Bessia C., Virelizier J.L., Arenzana-Seisdedos F., et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382 (1996) 833-835
13. Schols D., Struyf S., Van Damme J., Este J.A., Henson G., and De Clercq E. Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J Exp Med 186 (1997) 1383-1388
14. Schols D., Este J.A., Henson G., and De Clercq E. Bicyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor fusin/CXCR-4. Antiviral Res 35 (1997) 147-156
15. Donzella G.A., Schols D., Lin S.W., Este J.A., Nagashima K.A., Maddon P.J., et al. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat Med 4 (1998) 72-77
16. Hendrix C.W., Collier A.C., Lederman M.M., Schols D., Pollard R.B., Brown S., et al. Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 37 (2004) 1253-1262
17. Liles W.C., Broxmeyer H.E., Rodger E., Wood B., Hubel K., Cooper S., et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 102 (2003) 2728-2730
18. + hematopoietic progenitor cells by AMD3100, a CXCR4 antagonist. Support Cancer Ther 1 (2004) 165-172
19. + cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 22 (2004) 1095-1102
20. Matthys P., Hatse S., Vermeire K., Wuyts A., Bridger G., Henson G.W., et al. AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1 chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-γ receptor-deficient mice. J Immunol 167 (2001) 4686-4692
21. Lukacs N.W., Berlin A., Schols D., Skerlj R.T., and Bridger G. AMD3100, a CXCR4 antagonist, attenuates allergic lung inflammation and airway hyperactivity. Am J Pathol 160 (2002) 1353-1360
22. Baggiolini M., Dewald B., and Moser B. Interleukin-8 and related chemotactic cytokines-CXC and CC chemokines. Adv Immunol 55 (1994) 97-179
23. Murdoch C., and Finn A. Chemokine receptors and their role in inflammation and infectious diseases. Blood 95 (2000) 3032-3043
24. Coward P., Chan S.D., Wada H.G., Humphries G.M., and Conklin B.R. Chimeric G proteins allow a high-throughput signaling assay of Gi-coupled receptors. Anal Biochem 270 (1999) 242-248
25. Bridger G.J., Skerlj R.T., Thornton D., Padmanabhan S., Martellucci S.A., Henson G.W., et al. Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on the aromatic linker. J Med Chem 38 (1995) 366-378
26. Crump M.P., Gong J.H., 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 16 (1997) 6996-7007
27. Amara A., Lorthioir O., Valenzuela A., Magerus A., Thelen M., Montes M., et al. Stromal cell-derived factor-1α associates with heparan sulfates through the first β-strand of the chemokine. J Biol Chem 274 (1999) 23916-23925
28. Murphy P.M., Baggiolini M., Charo I.F., Hebert C.A., Horuk R., Matsushima K., et al. International union of pharmacology XXII. Nomenclature for chemokine receptors. Pharmacol Rev 52 (2000) 145-176
29. Frang H., Mukkala V.M., Syysto R., Ollikka P., Hurskainen P., Scheinin M., et al. Nonradioactive GTP binding assay to monitor activation of G protein-coupled receptors. Assay Drug Dev Technol 1 (2003) 275-280
30. Burger J.A., Burger M., and Kipps T.J. Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood 94 (1999) 3658-3667
31. Mohle R., Schittenhelm M., Failenschmid C., Bautz F., Kratz-Albers K., Serve H., et al. Functional response of leukaemic blasts to stromal cell-derived factor-1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia. Brit J Haematol 110 (2000) 563-572
32. Durig J., Schmucker U., and Duhrsen U. Differential expression of chemokine receptors in B cell malignancies. Leukemia 15 (2001) 752-756
33. Juarez J., Bradstock K.F., Gottlieb D.J., and Bendall L.J. Effects of inhibitors of the chemokine receptor CXCR4 on acute lymphoblastic leukemia cells in vitro. Leukemia 17 (2003) 1294-1300
34. Muller A., Homey B., Soto H., Ge N., Catron D., Buchanan M.E., et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 410 (2001) 50-56
35. Scotton C.J., Wilson J.L., Scott K., Stamp G., Wilbanks G.D., Fricker S., et al. Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res 62 (2002) 5930-5938
36. Rubin J.B., Kung A.L., Klein R.S., Chan J.A., Sun Y., Schmidt K., et al. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci USA 100 (2003) 13513-13518
37. Philips R., Burdick M.D., Lutz M., Belperio J.A., Keane M.P., and Strieter R.M. The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases. Am J Respir Crit Care Med 167 (2003) 1676-1686
38. Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol 14 (2004) 171-179
39. Buckley C.D., Amft N., Bradfield P.F., Pilling D., Ross E., Arenzana-Seisdedos F., et al. Persistent induction of the chemokine receptor CXCR4 by TGF-b 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium. J Immunol 165 (2000) 3423-3429
40. + T cell accumulation in rheumatoid arthritis synovium. J Immunol 165 (2000) 6590-6598
41. Gonzalo J.A., Lloyd C.M., Peled A., Delaney T., Coyle A.J., and Gutierrez-Ramos J.C. Critical involvement of the chemotactic axis CXCR4/stromal cell-derived factor-1α in the inflammatory component of allergic airway disease. J Immunol 165 (2000) 499-508
42. Di Salvo J., Koch G.E., Johnson K.E., Blake A.D., Daugherty B.L., DeMartino J.A., et al. The CXCR4 agonist ligand stromal derived factor-1 maintains high affinity for receptors in both Gα(i)-coupled and uncoupled states. Eur J Pharmacol 409 (2000) 143-154
43. Gerlach L.O., Skerlj R.T., Bridger G.J., and Schwartz T.W. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J Biol Chem 276 (2001) 14153-14160
44. Heveker N., Tissot M., Thuret A., Schneider-Mergener J., Alizon M., Roch M., et al. Pharmacological properties of peptides derived from stromal cell-derived factor 1: study on human polymorphonuclear cells. Mol Pharmacol 59 (2001) 1418-1425
45. Valenzuela-Fernandez A., Palanche T., Amara A., Magerus A., Altmeyer R., Delaunay T., et al. Optimal inhibition of X4 HIV isolates by the CXC chemokine stromal cell-derived factor 1α requires interaction with cell surface heparan sulfate proteoglycans. J Biol Chem 276 (2001) 26550-26558
46. Gupta S.K., Pillarisetti K., Thomas R.A., and Aiyar N. Pharmacological evidence for complex and multiple site interaction of CXCR4 with SDF-1α: implications for development of selective CXCR4 antagonists. Immunol Lett 78 (2001) 29-34
47. Balabanian K., Lagane B., Infantino S., Chow K.Y., Harriague J., Moepps B., et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T-lymphocytes. J Biol Chem 280 (2005) 35760-35766
48. Baribaud F., Edwards T.G., Sharron M., Brelot A., Heveker N., Price K., et al. Antigenically distinct conformations of CXCR4. J Virol 75 (2001) 8957-8967
49. Hatse S., Princen K., Bridger G., De Clercq E., and Schols D. Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4. FEBS Lett 527 (2002) 255-262
50. Zhang W.B., Navenot J.M., Haribabu B., Tamamura H., Hiramatu K., Omagari A., et al. A point mutation that confers constitutive activity to CXCR4 reveals that T140 is an inverse agonist and that AMD3100 and ALX40-4C are weak partial agonists. J Biol Chem 277 (2002) 24515-24521
51. Flomenberg N., Devine S.M., Dipersio J.F., Liesveld J.L., McCarty J.M., Rowley S.D., et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 106 (2005) 1867-1874