A future perspective on the development of chemokine receptor CXCR4 antagonists

Expert Opinion on Drug Discovery

Volumn 3, Issue 10, 2008, Pages 1155-1166

  Tamamura, Hirokazu ^a   Tsutsumi, Hiroshi ^a   Nomura, Wataru ^a   Tanaka, Tomohiro ^a   Fujii, Nobutaka ^b  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b KYOTO UNIVERSITY   (Japan)

Author keywords

AIDS; Cancer metastasis; Chemokine receptor; CXCR4 antagonist; FC131; HIV infection; Leukemia; Rheumatoid arthritis; T140; T22

Indexed keywords

4F BENZOYL TE14011; 4F BENZOYL TN14003; 8 [(4 AMINOBUTYL)(2 BENZIMIDAZOLYLMETHYL)AMINO] 1,2,3,4 TETRAHYDROQUINOLINE; [1 DEXTRO PHENYLALANINE (4 F) 5 ARGININE][CYCLO[1,2 ARGININE 3 [3 (2 NAPHTHYL)ALANINE] 4 GLYCINE DEXTRO 5 TYROSINE]]; [1 DEXTRO TYROSINE 5 ARGININE][CYCLO[1,2 ARGININE 3 [3 (2 NAPHTHYL)ALANINE] 4 GLYCINE DEXTRO 5 TYROSINE]]; [1 PHENYLALANINE (4 F)][CYCLO[ 1,2 ARGININE 3 [3 (2 NAPHTHYL)ALANINE] 4 GLYCINE DEXTRO 5 TYROSINE]]; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CXCR4; CHEMOKINE RECEPTOR CXCR4 ANTAGONIST; CS 3955; CYCLO[1 ARGININE 2 ARGININE 3 [3( 2 NAPHTHYL)ALANINE] 4 GLYCINE DEXTRO 5 TYROSINE]; CYCLO[1 METHIONYLARGINE 2 ARGININE 3 [3( 2 NAPHTHYL)ALANINE] 4 GLYCINE DEXTRO 5 TYROSINE]; DEXAMETHASONE; FC 122; FC 131; FC 401; FC 602; KRH 1636; KRH 2731; N [1,4,8,11 TETRAAZACYCLOTETRADECANYL 1,4 PHENYLENEBIS(METHYLENE)] 2 (AMINOMETHYL)PYRIDINE; PLERIXAFOR; POL 3026; POL3026; POLYLACTIC ACID; T 140; UNCLASSIFIED DRUG; VINCRISTINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; BINDING AFFINITY; BREAST CANCER; CANCER GROWTH; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED DRUG RELEASE; DRUG DESIGN; DRUG POTENTIATION; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMORAL IMMUNITY; HYPERSENSITIVITY REACTION; LUNG METASTASIS; LYMPHOCYTE PROLIFERATION; MOLECULAR SIZE; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; VIRUS INHIBITION;

EID: 55049086302     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460441.3.10.1155     Document Type: Review

References (85)

1. Tamamura H, Tsutsumi H. Specific probes for chemokine receptors. Chem Biol 2006;13:8-10
2. Tashiro K, Tada H, Heilker R, et al. Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science 1993;261:600-3
3. Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci USA 1994;91:2305-9
4. Oberlin E, Amara A, Bachelerie F, et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HTV-1. Nature 1996;382:833-5
5. Bleul CC, Farzan M, Choe H, et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 1996;382:829-33
6. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry co-factor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996;272:872-7
7. Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer a possible role for tumor progression. Clin Cancer Res 2000;6:3530-5
8. Geminder H, Sagi-Assif O, Goldberg L, et al. A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived. factor-1, in the development of bone marrow metastases in neuroblastoma. J Immunol 2001;167:4747-57
9. Müller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001;410:50-6
10. Robledo MM, Bartolome RA, Longo N, et al. Expression of functional chemokine receptors CXCR3 and CXCR4 on human melanoma cells. J Biol Chem 2001;276:45098-105
11. Sanz-Rodriguez F, Hidalgo A, Teixido J. Chcmokine stromal cell-derived factor-1α modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. Blood 2001;97:346-51
12. Scotton CJ, Wilson JL, Milliken D, et al. Epithelial cancer cell migration: a role for chemokine receptors? Cancer Res 2001;61:4961-5
13. Bertolini F, Dell'agnola C, Mancuso P, et al. CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin's lymphoma. Cancer Res 2002;62:3106-12
14. Kijima T, Maulik G, Ma PC, et al. Regulation of cellular proliferation, cytoskeletal function, and signal transduction through CXCR4 and c-Kit in small cell lung cancer cells. Cancer Res 2002;62:6304-11
15. Schrader AJ, Lechner O, Templin M, et al. CXCR4/CXCL12 expression and signaling in kidney cancer. Br J Cancer 2002;86:1250-6
16. Scotton CJ, Wilson JL, Scott K, et al. Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res 2002;62:5930-8
17. Taichman RS, Cooper C, Keller ET. et al. Use of the stromal cell-derived facror-1/CXCR4 pathway in prostate cancer matastasis to bone. Cancer Res 2002;62:1832-7
18. Burger M, Glodek A, Hartmann T, et al. Functional expression of CXCR4 (CD184) on small-cell lung cancer cells mediates migration, integrin activation, and adhesion to stromal cells. Oncogene 2003;22:8093-101
19. Rubin JB, Kung AL, Klein RS, et al. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci USA 2003;100:13513-8
20. Tamamura H, Hori A, Kanzaki N, et al. T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer. FEBS Lett 2003;550:79-83
21. Takenaga M, Tamamura H, Hiramatsu K, et al. A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma. Biochem Biophys Res Commun 2004;320:226-32
22. Mori T, Doi R, Koizumi K, et al. CXCR4 antagonist inhibits scromal cell-derived factor 1-induced migration and invasion of human pancreatic cancer. Mol Cancer Ther 2004;3:29-37
23. Piovan E, Tosello V, Indraccolo S, et al. Chemokine receptor expression in EBV-associated lymphoproliferation in Hu/SCID mice: implications for CXCL12/CXCR4 axis in lymphoma generation. Blood 2005;105:931-9
24. Zannettino ACW, Farrugia AN, Kortesidis A. et al. Elevated serum levels of SDF-1α are associated with increased osteoclast activity and osteolytic: bone disease in multiple myeloma patients. Cancer Res 2005;65:1700-9
25. Burger JA, Burger M, Kipps TJ. Chronic lymphocytic leukemia B cells express Functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood 1999;94:3658-67
26. Juarez J, Bradstock KR Gottlieb DJ, Bendall LJ. Effeccs of inhibitors of the chemokine receptor CXCR4 on acute lymphoblastic leukemia cells in vitro. Leukemia 2003;17:1294-300
27. Burger M, Hartmann T, Krome M, et al. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood 2005;106:1824-30
28. Spoo A, Lübbert M, Wierda WG, Burger JA. CXCR4 is a prognostic marker in acute myelogenous leukemia. Blood 2007;109:786-91
29. Nanki T, Hayashida K, El-Gabalawy HS, et al. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium. J Immunol 2000;165.6590-8
30. Balabanian K, Lagane B, Infantino S, et al. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem 2005;280:35760-6
31. Burns JM, Summers BC, Wang Y, et al. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development J Exp Med 2006;203:2201-13
32. Alkhatib G, Combadiere C, Broder CC, et al. A RANTES, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996;272:1955-8
33. Choe H, Farzan M, Sun Y, et al. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 1996;85:1135-48
34. Deng H, Liu R, Ellmeier W, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996;381:661-6
35. Doranz BJ, Rucker J, YI Y, et al. A dual-tropic primary HIV-1 isolate that uses fusin and the β-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1996;85:1149-58
36. Dragic T, Litwin V, Allaway GP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996;381:667-73
37. Nakamura T, Furunaka H, Miyata T, et al. Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus). J Biol Chem 1988;263:16709-13
38. Miyata T, Tokunaga F, Yoneya T, et al. Antimicrobial peptides, isolated from horseshoe crab hemocytes, tachyplesin II, and polyphemusins I and II: chemical structures and biological activity. J Biochem 1989;106:663-8
39. Masuda M, Nakashima H, Ueda T, et al. A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12, Lys7]-polyphemusin II). Biochem Biophys Res Commun 1992;189:845-50
40. Nakashima H, Masuda M, Murakami T, et al. Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22 ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion. Antimicrob Agents Chemother 1992;36:1249-55
41. Tamamura H, Xu Y, Hattori T, et al. A low molecular weight inhibitor against the chemokine receptor CXCR4: a strong anti-HIV peptide T140. Biochem Biophys Res Commun 1998;253:877-82
42. Murakami T, Nakajima T, Koyanagi Y, et al. A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. J Exp Med 1997;186:1389-93
43. Xu Y, Tamamura H, Arakaki R, et al. Marked increase in anti-HIV activity, as well as inhibitory activity against HIV entry mediated by CXCR4, linked to enhancement of the binding ability of tachyplesin analogs to CXCR4. AIDS Res Hum Retroviruses 1999;15:419-27
44. Murakami T, Zhang T-Y, Koyanagi Y, et al. Inhibitory mechanism of the CXCR4 antagonist T22 against human inummodeficiency virus type 1 infection. J Virol 1999;73:7489-96
45. Tamamura H. Sugioka M, Odagaki Y, et al. Conformational study of a highly specific CXCR4 inhibitor, T140, disclosing the dose proximity of its intrinsic pharmacophores associated with strong anti-HIV activity. Bioorg Med Chem Lett 2001;11:359-62, 2409
46. Tamamura H, Omagari A, Oishi S, et al. Pharmacophore identification of a specific CXCR4 inhibitor, T140, leads to development of effective and-HIV agents with very high selectivity indexes. Bioorg Med Chem Lett 2000;10:2633-7
47. Kanbara K, Sato S, Tanuma J, et al. Biological and genetic characterization of a human immunodeficiency virus strain resistant to CXCR4 antagonist T134. AIDS Res Hum Retroviruses 2001;17:615-22
48. Tamamura H, Omagari A, Hiramatsu K, et al. Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140. Bioorg Med Chem Lett 2001;11:1897-902
49. Tamamura H, Hiramatsu K, Kusano S, et al. Synthesis of potent CXCR4 inhibitors possessing low cytotoxicity and improved biostability based on T140 derivatives. Org Biomol Chem 2003;1:3656-62
50. Tamamura H, Hiramatsu K, Mizumoto M, et al. Enhancement of the T140-based pharmacophores leads to the development of more potent and bio-stable CXCR4 antagonists. Org Biomol Chem 2003;1:3663-9
51. Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol 2004;14:171-9
52. Murakami T, Maki W, Cardones AR, et al. Expression of CXC chcmokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Res 2002;62:7328-34
53. Tamamura H, Fujisawa M, Hiramatsu K, et al. Identification of a CXCR4 antagonist, a T140 analog, as an anti-rheumatoid arthritis agent. FEBS Lett 2004;569:99-104
54. Fujii N, Oishi S, Hiramatsu K, et al. Molecular-size reduction of a potent CXCR4-chemokine antagonist using orthogonal combination of conformation- and sequence-based libraries. Angew Chem Int Ed Engl 2003;42:3251-3
55. Ueda S, Oishi S, Wang Z, et al. Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4 antagonists: disclosing the importance of side-chain and backbone functionalities. J Med Chem 2007;49:3412-5
56. Tamamura H, Esaka A, Ogawa T, et al. Structure-activity relationship studies on CXCR4 antagonists having cyclic pentapeptide scaffolds. Org Biomol Chem 2005;3:4392-4
57. Tamamura H, Tsutsumi H, Masuno H, et al. Development of a linear type of low molecular weight CXCR4 antagonists based on T140 analogs. Org Biomol Chem 2006;4:2354-7
58. Ueda S, Kato M, Inuki S, et al. Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach. Bioorg Med Chem Lett 2008;18:4124-9
59. Ojida A, Mito-Oka Y, Sada K, et al. Molecular recognition and fluorescence sensing of monophosphorylated peptides in aqueous solution by bis(zinc(ii)-dipicolylamine)-based artificial receptors. J Am Chem Soc 2004;126:2454-63
60. Tamamura H, Ojida A, Ogawa T, et al. Identification of a new class of low molecular weight antagonists against the chemokine receptor CXCR4 having the dipicolylamine-zinc(ii) complex structure. J Med Chem 2006;49:3412-5
61. Demarco SJ, Henze H, Lederer A, et al. Discovery of novel, highly potent and selective beta-hairpin mimetic CXCR4 inhibitors with excellent anti-HIV activity and pharmacokinetic profiles. Bioorg Med Chem 2006;14:8396-404
62. Mastrolorenzo A, ScozzaFava A, Supuran CT. Small molecule antagonists of chemokine receptors as emerging and-HIV agents. Expert Opin Ther Patents 2001;11:1245-52
63. Scozzafava A, Mastrolorenzo A, Supuran CT. Non-peptidic chemokine receptors antagonists as emerging and-HIV agents. J Enzyme Inhib Med Chem 2002;17:69-76
64. Schols D, Struyf S, Van Damme J, et al. Inhibition of T-Eropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J Exp Med 1997;186:1383-8
65. De Clercq E. New anti-HIV agents and targets. Med Res Rev 2002;22:531-65
66. Vermeire K, Hatse S, Princen K, et al. Virus resistance to the CXCR4 inhibitor AMD070 develops slowly and does not induce a co-receptor switch. Antiviral Res 2004;62:A42-3
67. Gerlach LO, Jakobsen JS, Jensen KP, et al. Metal ion enhanced binding of AMD3100 to Asp262 in the CXCR4 receptor. Biochemistry 2003;42:710-7
68. Seibert C, Sakmar TP. Small-molecule antagonists of CCR5 and CXCR4: a promising new class of and-HIV-1 drugs. Curr Pharm Des 2004;10:2041-62
69. Doranz BJ, Grovit-Ferbas K, Sharron MP, et al. A small-molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor. J Exp Med 1997;186:1395-400
70. Cabrera C, Gutierrez A, Barretina J, et al. Anti-HIV activity of a novel aminoglycoside-arginine conjugate. Antiviral Res 2002;53:1-8
71. Cabrera C, Gutierrez A, Blanco J, et al. Anti-human immunodeficiency virus activity of novel aminoglycoside-arginine conjugates at early stages of infection. AIDS Res Hum Retroviruses 2000;16:627-34
72. Daelemans D, Schols D, Witvrouw M, et al. A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry. Mol Pharmacol 2000;57:116-24
73. Howard Omz, Oppenheim JJ, Hollingshead MG, et al. Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that interferes with chemokine receptor function: a candidate for chemotherapeutic and microbicidal application. J Med Chem 1998:41:2184-93
74. Zhan W, Liang Z, Zhu A, et al. Discovery of small molecule CXCR4 antagonists. J Med Chem 2007;50:5655-64
75. Liu D-Y, Ye J-T, Yang W-H, et al. Ampelopsin, a small molecule inhibitor of HIV-1 infection targeting HIV entry. Biomed Environ Sci 2004;17:153-64
76. Daoudi J-M, Greiner J, Aubertin A-M, Vierling P. New bicyclam-GalCer analogue conjugates: synthesis and in vitro anti-HIV activity. Bioorg Med Chem Lett 2004;14:495-8
77. Ichiyama K, Yokoyama-Kumakura S, Tanaka Y, et al. A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective and-HTV-1 activity. Proc Natl Acad Sci USA 2003;100:4185-90
78. Kureha Chemical Industry Co. Ltd. Yamazaki T, Saitou A, Ono M, et al. Novel nitrogenous compound and use thereof. WO029218; 2003
79. Kureha Chemical Industry Co. Ltd. Yamazaki T, Kikumoto S, Ono M, et al. Amine compound and use thereof. WO024697; 2004
80. Zou Y-R, Kottmann AH, Kuroda M, et al. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998;393:595-9
81. Nakata H, Steinberg SM, Koh Y, et al. Potent synergistic anti-human immunodeficiency virus (HIV) effects using combinations of the CCR5 inhibitor aplaviroc with other anti-HIV drugs. Antimicrob Agents Chemother 2008;52:2111-9
82. Abraham M, Biyder K, Begin M, et al. Enhanced unique pattern of hematopoietic cell mobilization induced by the CXCR4 antagonist 4F-benzoyl-TN14003. Stem Cells 2007;25:2158-66
83. Broxmeyer HE, Orschell CM, Wade Clapp D, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 2005;201:1307-18
84. Liles WC, Broxmeyer HE, Rodger E, et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 2003;102:2728-30
85. Trent JO, Wang Z, Murray JL, et al. Lipid bilayer simulations of CXCR4 with inverse agonists and weak partial aganists. J Biol Chem 2003;278:47136-44