title: AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor.
abstract: The bicyclam AMD3100 (formula weight 830) blocks HIV-1 entry and membrane fusion via the CXCR4 co-receptor, but not via CCR5. AMD3100 prevents monoclonal antibody 12G5 from binding to CXCR4, but has no effect on binding of monoclonal antibody 2D7 to CCR5. It also inhibits binding of the CXC-chemokine, SDF-1alpha, to CXCR4 and subsequent signal transduction, but does not itself cause signaling and has no effect on RANTES signaling via CCR5. Thus, AMD3100 prevents CXCR4 functioning as both a HIV-1 co-receptor and a CXC-chemokine receptor. Development of small molecule inhibitors of HIV-1 entry is feasible.
authors.affiliation: The Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Donzella
authors.forename: D
authors.initials: D
authors.lastname: Schols
authors.forename: S W
authors.initials: SW
authors.lastname: Lin
authors.forename: J A
authors.initials: JA
authors.lastname: Esté
authors.forename: K A
authors.initials: KA
authors.lastname: Nagashima
authors.forename: P J
authors.initials: PJ
authors.lastname: Maddon
authors.forename: G P
authors.initials: GP
authors.lastname: Allaway
authors.forename: T P
authors.initials: TP
authors.lastname: Sakmar
authors.forename: G
authors.initials: G
authors.lastname: Henson
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001596:Benzylamines; D015704:CD4 Antigens / Q000276:immunology / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002459:Cell Fusion; D002460:Cell Line; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000080027:Cyclams; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008561:Membrane Fusion / Q000187:drug effects; D019713:Receptors, CCR5 / Q000502:physiology; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D001596:Benzylamines; D015704:CD4 Antigens; C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000080027:Cyclams; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D006571:Heterocyclic Compounds; D007376:Interleukin-2; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D013004:Somatostatin; D002217:Carbachol; C088327:plerixafor; D002118:Calcium