HIV-1 entry inhibitors: Closing the front door

Expert Opinion on Therapeutic Targets

Volumn 8, Issue 2, 2004, Pages 65-78

  Tomkowicz, Brian ^a   Collman, Ronald G ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

CC chemokine receptor 5 (CCR5); CD4; Chemokine receptor; CXC chemokine receptor 4 (CXCR4); Fusion; Gp120; Viral entry

Indexed keywords

1 ACETYL N [3 [4 (4 CARBAMOYLBENZYL) 1 PIPERIDINYL]PROPYL] N (3 CHLORO 4 METHYLPHENYL) 4 PIPERIDINECARBOXAMIDE; 1 BENZOYL 4 [(4,7 DIMETHOXY 1H PYRROLO[2,3 C]PYRIDIN 3 YL)OXOACETYL]PIPERAZINE; 1,1' [1,4 PHENYLENEBIS(METHYLENE)]BIS(1,4,8,11 TETRAAZACYCLOTETRADECANE); 4 [(4 BROMOPHENYL)(ETHOXYIMINO)METHYL] 1' [(2,4 DIMETHYL 3 PYRIDINYL)CARBONYL] 4' METHYL 1,4' BIPIPERIDINE; 4 BENZOYL 1 [(4 METHOXY 1H PYRROLO[2,3 B]PYRIDIN 3 YL)OXOACETYL] 2 METHYLPIPERAZINE; ALPHA N ACETYLNONA DEXTRO ARGININE AMIDE; AMD 070; ANTIRETROVIRUS AGENT; APLAVIROC; CD4 ANTIGEN; CD4 IMMUNOGLOBULIN G2; CHEMOKINE RECEPTOR; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; CYCLOTRIAZADISULFONAMIDE; DEXTRAN SULFATE; E 913; ENFUVIRTIDE; GLYCOPROTEIN GP 120; KRH 1636; MARAVIROC; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; PRO 140; RANTES; SURAMIN; T 1249; T 22; UNCLASSIFIED DRUG; VIRUS ENVELOPE PROTEIN;

ANTIGEN BINDING; ANTIVIRAL ACTIVITY; CLINICAL TRIAL; DRUG HALF LIFE; DRUG MECHANISM; DRUG TARGETING; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIFE CYCLE; NONHUMAN; QT PROLONGATION; REVIEW; SIDE EFFECT; T LYMPHOCYTE ACTIVATION; VIRUS ENVELOPE; VIRUS LOAD;

ANIMALS; HIV FUSION INHIBITORS; HIV INFECTIONS; HIV-1; HUMANS;

EID: 1842843662     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.8.2.65     Document Type: Review

References (138)

1. BERGER EA, MURPHY PM, FARBER JM: Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. (1999) 17.657-700.
2. ECKERT DM, KIM PS: Mechanisms of viral membrane fusion and its inhibition. Annu. Rev. Biochem. (2001) 70:777-810.
3. ZIMMERBERG J, CHERNOMORDIK LV: Membrane fusion. Adv. Drug Deliv. Rev. (1999) 38:197-205.
4. DOMS RW, MOORE JP: HIV-1 membrane fusion: targets of opportunity. J. Cell Biol. (2000) 151:F9-14.
5. LEE C, LIU QH, TOMKOWICZ B et al.: Macrophage activation through CCR5- and CXCR4-mediated gp 120-elicited signaling pathways. J. Leukoc. Biol. (2003) 74:676-682.
6. MARINISSEN MJ, GUTKIND JS: G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol. Sci. (2001) 22:368-376.
7. FENG Y, BRODER CC, KENNEDY PE, BERGER EA: HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science (1996) 272:872-877.
8. 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) 85:1149-1158.
9. DENG H, LIU R, ELLMEIER W et al.: Identification of a major co-receptor for primary isolates of HIV-1. Nature (1996) 381:661-666.
10. VAN'T WOUT AB, KOOTSTRA NA, MULDER-KAMPINGA GA et al.: Macrophage-tropic variants initiate human immunodeficiency virus Type 1 infection after sexual, parenteral, and vertical transmission. J. Clin. Invest. (1994) 94:2060-2067.
11. ZHU T, MO H, WANG N et al.: Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science (1993) 261:1179-1181.
12. CONNOR RI, SHERIDAN KE, CERADINI D, CHOE S, LANDAU NR: Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J. Exp. Med. (1997) 185:621-628.
13. SCHUITEMAKER H, KOOTSTRA NA, DE GOEDE RE et al.: Monocytotropic human immunodeficiency virus Type 1 (HIV-1) variants detectable in all stages of HIV-1 infection lack T-cell line tropism and syncytium-inducing ability in primary T-cell culture. J. Virol. (1991) 65:356-363.
14. COLLMAN RG, YI Y, LIU QH, FREEDMAN BD: Chemokine signaling and HIV-1 fusion mediated by macrophage CXCR4: implications for target cell tropism. J. Leukoc. Biol. (2000) 68:318-323.
15. LIU R, PAXTON WA, CHOE S et al.: Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell (1996) 86:367-377.
16. SAMSON M, LIBERT F, DORANZ BJ et al.: Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature (1996) 382:722-725.
17. BENKIRANE M, JIN DY, CHUN RF, KOUP RA, JEANG KT: Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5Δ32. J. Biol. Chem. (1997) 272:30603-30606.
18. DEAN M, CARRINGTON M, WINKLER C et al.: Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science (1996) 273:1856-1862.
19. BASHIROVA AA, GEIJTENBEEK TB, VAN DUIJNHOVEN GC et al.: A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J. Exp. Med. (2001) 193:671-678.
20. GEIJTENBEEK TB, KWON DS, TORENSMA R et al.: DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell (2000) 100:587-597.
21. GEIJTENBEEK TB, TORENSMA R, VAN VLIET SJ et al.: Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell (2000) 100:575-585.
22. + T cells. Science (1992) 257:383-387.
23. FEINBERG H, MITCHELL DA, DRICKAMER K, WEIS WI: Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR. Science (2001) 294:2163-2166.
24. KAZMIERSKI W, BIFULCO N, YANG H et al.: Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors. Bioorg. Med. Chem. (2003) 11:2663-2676.
25. MOORE JP, DOMS RW: The entry of entry inhibitors: a fusion of science and medicine. Proc. Natl. Acad. Sci. USA (2003) 100:10598-10602.
26. KILBY JM, ERON JJ: Novel therapies based on mechanisms of HIV-1 cell entry. N. Engl. J. Med. (2003) 348:2228-2238.
27. STARR-SPIRES LD, COLLMAN RG: HIV-1 entry and entry inhibitors as therapeutic agents. Clin. Lab. Med. (2002) 22:681-701.
28. NOVINA CD, MURRAY MF, DYKXHOORN DM et al.: siRNA-directed inhibition of HIV-1 infection. Nat. Med. (2002) 8:681-686.
29. CHEN JD, BAI X, YANG AG, CONG Y, CHEN SY: Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy. Nat. Med. (1997) 3:1110-1116.
30. SMITH DH, BYRN RA, MARSTERS SA et al.: Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen. Science (1987) 238:1704-1707.
31. SCHOOLEY RT, MERIGAN TC, GAUT P et al.: Recombinant soluble CD4 therapy in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A Phase I-II escalating dosage trial. Ann. Intern. Med. (1990) 112:247-253.
32. SCHACKER T, COLLIER AC, COOMBS R et al.: Phase I study of high-dose, intravenous rsCD4 in subjects with advanced HIV-1 infection. J. Acquir. Immune Defic. Syndr. (1995) 9:145-152.
33. DAAR ES, LI XL, MOUDGIL T, HO DD: High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus Type 1 isolates. Proc. Natl. Acad. Sci. USA (1990) 87:6574-6578.
34. MOORE JP, MCKEATING JA, HUANG YX, ASHKENAZI A, HO DD: Virions of primary human immunodeficiency virus Type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J. Virol. (1992) 66:235-243.
35. TRKOLA A, POMALES AB, YUAN H et al.: Cross-clade neutralization of primary isolates of human immunodeficiency virus Type 1 by human monoclonal antibodies and tetrameric CD4-IgG. J. Virol. (1995) 69:6609-6617.
36. 2 protects Hu-PBL-SCID mice against challenge by primary human immunodeficiency virus Type 1 isolates. J. Virol. (1998) 72:3475-3478.
37. JACOBSON JM, LOWY I, FLETCHER CV et al.: Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) Type 1 entry inhibitor PRO 542 in HIV-infected adults. J. Infect. Dis. (2000) 182:326-329.
38. 2 in human immunodeficiency virus Type 1 -infected children: Phase I/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team. J. Infect. Dis. (2000) 182:1774-1779.
39. WANG T, ZHANG Z, WALLACE OB et al.: Discovery of 4-benzoyl-1-[(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2-(R)- methylpiperazine (BMS-378806): a novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions. J. Med. Chem. (2003) 46:4236-4239.
40. GUO Q, HO HT, DICKER I et al.: Biochemical and genetic characterizations of a novel human immunodeficiency virus Type 1 inhibitor that blocks gp120-CD4 interactions. J. Virol. (2003) 77:10528-10536.
41. LIN PF, BLAIR W, WANG T et al.: A small molecule HIV-1 inhibitor that targets the HIV-1 envelope and inhibits CD4 receptor binding. Proc. Natl. Acad. Sci. USA (2003) 100:11013-11018.
42. HANNA G, YAN JH, FISKE W et al.: Safety, tolerability, and pharmacokinetics of a novel, small-molecule HIV-1 attachment inhibitor, BMS-488043, after single and multiple oral doses in healthy subjects. In: Abstracts of the 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, USA. February 8-11 (2004):535.
43. HANNA G, LALEZARI J, HELLINGER J et al.: Antiviral activity, safety, and tolerability of a novel, oral small-molecule HIV-1 attachment inhibitor, BMS-488043, in HIV1-infected subjects. In: Abstracts of the 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, USA. February 8-11 (2004):141.
44. LIN PF, HO HT, GONG YF et al.: Characterization of a small molecule HIV-1 attachment inhibitor BMS-488043: virology, resistance and mechanism of action. In: Abstracts of the 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, USA. February 8-11 (2004):534.
45. VERMEIRE K, BELL TW, CHOI HJ et al.: The anti-HIV potency of cyclotriazadisulfonamide analogs is directly correlated with their ability to down-modulate the CD4 receptor. Mol. Pharmacol. (2003) 63:203-210.
46. VERMEIRE K, ZHANG Y, PRINCEN K et al.: CADA inhibits human immunodeficiency virus and human herpesvirus 7 replication by down-modulation of the cellular CD4 receptor. Virology (2002) 302:342-353.
47. CRUIKSHANK WW, KORNFELD H, CENTER DM: Interleukin-16. J. Leukoc. Biol. (2000) 67:757-766.
48. + cells. Science (1988) 240:646-649.
49. SCHOLS D, BABA M, PAUWELS R, DESMYTER J, DE CLERCQ E: Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor. Proc. Natl. Acad. Sci. USA (1989) 86:3322-3326.
50. YAO XJ, WAINBERG MA, POLLAK M: The inhibitory effects of suramin on HIV-1 are attenuated in the presence of albumin. AIDS (1991) 5:1389-1391.
51. WYATT R, KWONG PD, DESJARDINS E et al.: The antigenic structure of the HIV gp120 envelope glycoprotein. Nature (1998) 393:705-711.
52. RICHMAN DD, WRIN T, LITTLE SJ, PETROPOULOS CJ: Rapid evolution of the neutralizing antibody response to HIV Type 1 infection. Proc. Natl. Acad. Sci. USA (2003) 100:4144-4149.
53. WEI X, DECKER JM, WANG S et al.: Antibody neutralization and escape by HIV-1. Nature (2003) 422:307-312.
54. LABRIJN AF, POIGNARD P, RAJA A et al.: Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary human immunodeficiency virus Type 1. J. Virol. (2003) 77:10557-10565.
55. REITTER JN, MEANS RE, DESROSIERS RC: A role for carbohydrates in immune evasion in AIDS. Nat. Med. (1998) 4:679-684.
56. KOCH M, PANCERA M, KWONG PD et al.: Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition. Virology (2003) 313:387-400.
57. ZOLLA-PAZNER S: Identifying epitopes of HIV-1 that induce protective immunity. Nat. Rev. Immunol. (2004) 4:199-210.
58. BURTON DR, DESROSIERS RC, DOMS RW et al.: HIV vaccine design and the neutralizing antibody problem. Nat. Immunol. (2004) 5:233-236.
59. HUANG Y, PAXTON WA, WOLINSKY SM et al.: The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat. Med. (1996) 2:1240-1243.
60. + T cells. Science (1995) 270:1811-1815.
61. MACK M, LUCKOW B, NELSON PJ et al.: Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity. J. Exp. Med. (1998) 187:1215-1224.
62. PASTORE C, PICCHIO GR, GALIMI F et al.: Two mechanisms for human immunodeficiency virus Type 1 inhibition by N-terminal modifications of RANTES. Antimicrob. Agents Chemother. (2003) 47:509-517.
63. SIMMONS G, REEVES JD, HIBBITTS S et al.: Co-receptor use by HIV and inhibition of HIV infection by chemokine receptor ligands. Immunol. Rev. (2000) 177:112-126.
64. BABA M, NISHIMURA O, KANZAKI N et al.: A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. USA (1999) 96:5698-5703.
65. DRAGIC T, TRKOLA A, THOMPSON DA et al.: A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc. Natl. Acad. Sci. USA (2000) 97:5639-5644.
66. LIZAWA Y, KANZAKI N, TAKASHIMA K: Anti-viral activity of TAK-220, a small molecule CCR5 antagonist. In: Abstracts of the 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA. February 10-14 (2003):11.
67. TREMBLAY CL, GIGUEL F, HICKS JL et al.: TAK-220, a novel small molecule inhibitor of CCR5 has favorable anti-HIV interactions with other anti-retrovirals in vitro. In: Abstracts of the 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA. February 10-14 (2003):562.
68. STRIZKI JM, XU S, WAGNER NE et al.: SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc. Natl. Acad. Sci. USA (2001) 98:12718-12723.
69. TAGAT JR, MCCOMBIE SW, STEENSMA RW et al.: Piperazine-based CCR5 antagonists as HIV-1 inhibitors. I: 2(S)-methyl piperazine as a key pharmacophore element. Bioorg. Med. Chem. Lett. (2001) 11:2143-2146.
70. TSAMIS F, GAVRILOV S, KAJUMO F et al.: Analysis of the mechanism by which the small-molecule CCR5 antagonists SCH-351125 and SCH-350581 inhibit human immunodeficiency virus Type 1 entry. J. Virol. (2003) 77:5201-5208.
71. REYNES J, ROUZIER R, KANOUNI T et al.: SCH C: safety and antiviral effects of a CCR5 receptor antagonist in HIV-1-infected subjects. In: Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, USA. February 24-28 (2002):1.
72. CHEN Z, HU B, HUANG W et al.: HIV-1 mutants less susceptible to SCH-D, a novel small-molecule antagonist of CCR5. In: Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, USA. February 24-28 (2002):396-T.
73. SCHURMANN D, ROUZIER R, NOUGAREDE R et al.: SCH D: antiviral activity of a CCR5 receptor antagonist. In: Abstracts of the 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, CA, USA. February 8-11 (2004):140LB.
74. DORR P, MACARTNEY M, RICKETT G et al.: UK-427,857, a novel small molecule hiv entry inhibitor is a specific antagonist of the chemokine receptor CCR5. In: Abstracts of the 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA. February 10-14 (2003):12.
75. MACARTNEY MJ et al.: In vitro antiviral profile of entry inhibitor UK-427,857. In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA. September 14-17 (2003):H-875.
76. NAPIER C, DORR P, GLADUE R et al.: The preclinical pharmacokinetics and safety pharmacology of the anti-HIV CCR antagonist, UK-427,857. In: Abstracts of the 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA. February 10-14 (2003):546-A.
77. POZNIAK AL et al.: Effect of short-term monotherapy with UK-427,857 on viral load in HIV-infected patients. In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA. September 14-17 (2003):H-443.
78. MAEDA K, YOSHIMURA K, SHIBAYAMA S et al.: Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J. Biol. Chem. (2001) 276:35194-35200.
79. MAEDA K, NAKATA H, MIYAKAWA T et al.: CCR5 binding profiles of AF602/ONO-4128, a novel HIV-specific and potent anti-HIV spiroketopiperazine (SDP) derivative, differ from those other existing CCR5 inhibitors. In: Abstracts of the 2nd IAS Conference on HIV Pathogenesis and Treatment. Paris, France. July 13-16 (2003):531.
80. LYNCH CL, HALE JJ, BUDHU RJ et al.: CCR5 antagonists: 3-(pyrrolidin-1-yl)propionic acid analogues with potent anti-HIV activity. Org. Lett. (2003) 5:2473-2475.
81. VEAZEY RS, KLASSE PJ, KETAS TJ et al.: Use of a small molecule CCR5 inhibitor in macaques to treat simian immunodeficiency virus infection or prevent simian-human immunodeficiency virus infection. J. Exp. Med. (2003) 198:1551-1562.
82. FRANTI M, NAGASHIMA KA, MADDON PJ et al.: The CCR5 co-receptor inhibitor PRO 140 effectively controls established HIV-1 infection in vivo. In: Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, USA. February 24-28 (2002):403-T.
83. OLSON WC, GARDNER JP, KETAS TJ: Inhibition of HIV-1 entry without coreceptor antagonism by the humanized anti-CCR5 antibody PRO 140. In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego, CA, USA. September 27-31 (2002):H-178.
84. TRKOLA A, KETAS TJ, NAGASHIMA KA et al.: Potent, broad-spectrum inhibition of human immunodeficiency virus Type 1 by the CCR5 monoclonal antibody PRO 140. J. Virol. (2001) 75:579-588.
85. CORMIER EG, KETAS TJ, SULLIVAN BM: Baseline viral susceptibility to the CCR5 co-receptor inhibitor PRO 140. In: Abstracts of the 2nd IAS Conference on HIV Pathogenesis and Treatment. Paris, France. July 13-16 (2003):530.
86. ZOU YR, KOTTMANN AH, KURODA M, TANIUCHI I, LITTMAN DR: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature (1998) 393:595-599.
87. TACHIBANA K, HIROTA S, IIZASA H et al.: The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature (1998) 393:591-594.
88. CAMPBELL DJ, KIM CH, BUTCHER EC: Chemokines in the systemic organization of immunity. Immunol. Rev. (2003) 195:58-71.
89. SCHOLS D, STRUYF S, VAN DAMME J et al.: Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J. Exp. Med. (1997) 186:1383-1388.
90. DE CLERCQ E: The bicyclam AMD3100 story. Nat. Rev. Drug Discov. (2003) 2:581-587.
91. DONZELLA GA, SCHOLS D, LIN SW et al.: AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat. Med. (1998) 4:72-77.
92. DATEMA R, RABIN L, HINCENBERGS M et al.: Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry. Antimicrob. Agents Chemother. (1996) 40:750-754.
93. HENDRIX CW, FLEXNER C, MACFARLAND RT et al.: Pharmacokinetics and safety of AMD-3100, a novel antagonist of the CXCR-4 chemokine receptor, in human volunteers. Antimicrob. Agents Chemother. (2000) 44:1667-1673.
94. SCHOLS D, CLAES S, DE CLERCQ E et al.: AMD-3100, a CXCR4 antagonist, reduced HIV viral load and X4 viral levels in humans. In: Abstracts of the 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, USA. February 24-28 (2002):2.
95. LILES WC, BROXMEYER HE, RODGER E et al.: Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood (2003) 102:2728-2730.
96. SCHOLS D, CLAES S, HATSE S et al.: Anti-HIV activity profile of AMD070, an orally bioavailable CXCR4 antagonist. In: Abstracts of the 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, USA. February 10-14 (2003):563.
97. ICHIYAMA K, YOKOYAMA-KUMAKURA S, TANAKA Y et al.: A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity. Proc. Natl. Acad. Sci. USA (2003) 100:4185-4190.
98. 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) 186:1389-1393.
99. MURAKAMI T, ZHANG TY, KOYANAGI Y et al.: Inhibitory mechanism of the CXCR4 antagonist T22 against human immunodeficiency virus Type 1 infection. J. Virol. (1999) 73:7489-7496.
100. 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) 1:3663-3669.
101. 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) 1:3656-3662.
102. ARAKAKI R, TAMAMURA H, PREMANATHAN M et al.: T134, a small-molecule CXCR4 inhibitor, has no cross-drug resistance with AMD3100, a CXCR4 antagonist with a different structure. J. Virol. (1999) 73:1719-1723.
103. 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) 186:1395-1400.
104. LUO Z, ZHOU N, LUO J, HALL JW, HUANG Z: The role of positively charged residues in CXCR4 recognition probed with synthetic peptides. Biochem. Biophys. Res. Commun. (1999) 263:691-695.
105. DORANZ BJ, FILION LG, DIAZ-MITOMA F et al.: Safe use of the CXCR4 inhibitor ALX40-4C in humans. AIDS Res. Hum. Retroviruses (2001) 17:475-486.
106. YANG OO, SWANBERG SL, LU Z et al.: Enhanced inhibition of human immunodeficiency virus Type 1 by Met-stromal-derived factor 1β correlates with down-modulation of CXCR4. J. Virol. (1999) 73:4582-4589.
107. CHEN CH, MATTHEWS TJ, MCDANAL CB, BOLOGNESI DP, GREENBERG ML: A molecular clasp in the human immunodeficiency virus (HIV) Type 1 TM protein determines the anti-HIV activity of gp41 derivatives: implication for viral fusion. J. Virol. (1995) 69:3771-3777.
108. KILBY JM, HOPKINS S, VENETTA TM et al.: Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat. Med. (1998) 4:1302-1307.
109. LAZZARIN A, CLOTET B, COOPER D et al.: Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N. Engl. J. Med. (2003) 348:2186-2195.
110. LALEZARI JP, HENRY K, O'HEARN M et al.: Enfuvirtide, in HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N. Engl. J. Med. (2003) 348:2175-2185.
111. ERON JJ, MERIGAN TC, KILBY M et al.: A 14-day assessment of the safety, pharmacokinetics, and antiviral activity of T-1249, a peptide inhibitor of membrane fusion. In: Abstracts of the 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, USA. February 4-8 (2001):14.
112. REEVES JD, GALLO SA, AHMAD N et al.: Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc. Natl. Acad. Sci. USA (2002) 99:16249-16254.
113. DERDEYN CA, DECKER JM, SFAKIANOS JN et al.: Sensitivity of human immunodeficiency virus Type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120. J. Virol. (2000) 74:8358-8367.
114. ROOT MJ, KAY MS, KIM PS: Protein design of an HIV-1 entry inhibitor. Science (2001) 291:884-888.
115. TREMBLAY CL, GIGUEL F, KOLLMANN C et al.: Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5 antagonist, with other antiretroviral agents in vitro. Antimicrob. Agents Chemother. (2002) 46:1336-1339.
116. SINGH A, COLLMAN RG: Heterogeneous spectrum of coreceptor usage among variants within a dualtropic human immunodeficiency virus Type 1 primary-isolate quasispecies. J. Virol. (2000) 74:10229-10235.
117. TRKOLA A, KUHMANN SE, STRIZKI JM et al.: HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc. Natl. Acad. Sci. USA (2002) 99-395-400.
118. MOSIER DE, PICCHIO GR, GUILIZIA RJ et al.: Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency virus Type 1 infection in vivo or rapidly select for CXCR4-using variants. J. Virol. (1999) 73:3544-3550.
119. + T lymphocytes primed by myeloid or plasmacytoid dendritic cells. Eur. J. Immunol. (2003) 33:474-482.
120. LEE S, TIFFANY HL, KING L et al.: CCR8 on human thymocytes functions as a human immunodeficiency virus Type 1 coreceptor. J. Virol. (2000) 74:6946-6952.
121. CHEN Z, KWON D, JIN Z et al.: Natural infection of a homozygous δ24 CCR5 red-capped mangabey with an R2b-tropic simian immunodeficiency virus. J. Exp. Med. (1998) 188:2057-2065.
122. ZHANG YJ, MOORE JP: Will multiple coreceptors need to be targeted by inhibitors of human immunodeficiency virus Type 1 entry? J. Virol. (1999) 73:3443-3448.
123. RESCH W, HOFFMAN N, SWANSTROM R: Improved success of phenotype prediction of the human immunodeficiency virus Type 1 from envelope variable loop 3 sequence using neural networks. Virology (2001) 288:51-62.
124. LABROSSE B, LABERNARDIERE JL, DAM E et al.: Baseline susceptibility of primary human immunodeficiency virus Type 1 to entry inhibitors. J. Virol. (2003) 77:1610-1613.
125. TANG J, RIVERS C, KARITA E et al.: Allelic variants of human β-chemokine receptor 5 (CCR5) promoter: evolutionary relationships and predictable associations with HIV-1 disease progression. Genes Immun. (1999) 1:20-27.
126. BELNOUE E, KAYIBANDA M, DESCHEMIN JC et al.: CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood (2003) 101:4253-4259.
127. + T cells following coronavirus infection of the central nervous system. Virology (2003) 312:407-414.
128. (+) T cells during virus-induced central nervous system disease. J. Virol. (2003) 77:191-198.
129. LUANGSAY S, KASPER LH, RACHINEL N et al.: CCR5 mediates specific migration of Toxoplasma gandii-primed CD8 lymphocytes to inflammatory intestinal epithelial cells. Gastroenterology (2003) 125:491-500.
130. HONCZARENKO M, LE Y, GLODEK AM et al.: CCR5-binding chemokines modulate CXCL12 (SDF-1)-induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor. Blood (2002) 100:2321-2329.
131. LAPIDOT T, KOLLET O: The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia (2002) 16:1992-2003.
132. ZHANG WB, NAVENOT JM, HARIBABU B 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. (2002) 277:24515-24521.
133. ESSER MT, MORI T, MONDOR I et al.: Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus Type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120. J. Virol. (1999) 73:4360-4371.
134. TSAI CC, EMAU P, JIANG Y et al.: Cyanovirin-N gel as a topical microbicide prevents rectal transmission of SHIV89.6P in macaques. AIDS Res. Hum. Retroviruses (2003) 19:535-541.
135. CHANG TL, CHANG CH, SIMPSON DA et al.: Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. Proc. Natl. Acad. Sci. USA (2003) 100:11672-11677.
136. YANG YF, MUKAI T, GAO P et al.: A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T cell migration without affecting anti-collagen T cell responses. Eur. J. Immunol. (2002) 32:2124-2132.
137. 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) 100:13513-13518.
138. 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.