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PMID: 9427609 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor.

Nature medicine ·Vol. 4 ·No. 1 ·1998-01-00 ·Pages 72-7

Donzella GA, Schols D, Lin SW, Esté JA, Nagashima KA, Maddon PJ, Allaway GP, Sakmar TP, Henson G, De Clercq E, Moore JP

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.

MeSH Terms

Anti-HIV Agents/pharmacology Antibodies, Monoclonal/pharmacology Benzylamines CD4 Antigens/immunology,physiology CD4-Positive T-Lymphocytes/drug effects,physiology,virology Calcium/metabolism Carbachol/pharmacology Cell Fusion Cell Line Cells, Cultured Chemokine CCL5/pharmacology Chemokine CXCL12 Chemokines, CXC Cyclams Cytokines/metabolism,pharmacology HIV Envelope Protein gp120/drug effects,metabolism HIV-1/drug effects,physiology Heterocyclic Compounds/pharmacology Humans Interleukin-2/pharmacology Kinetics Membrane Fusion/drug effects Receptors, CCR5/physiology Receptors, CXCR4/drug effects,immunology,physiology Signal Transduction/drug effects Somatostatin/pharmacology

Chemicals

Anti-HIV Agents Antibodies, Monoclonal Benzylamines CD4 Antigens CXCL12 protein, human Chemokine CCL5 Chemokine CXCL12 Chemokines, CXC Cyclams Cytokines HIV Envelope Protein gp120 Heterocyclic Compounds Interleukin-2 Receptors, CCR5 Receptors, CXCR4 Somatostatin Carbachol plerixafor Calcium

Authors & Affiliations

11 authors, click to expand affiliations / ORCID

Donzella G A

The Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.

Schols D

Lin S W

Esté J A

Nagashima K A

Maddon P J

Allaway G P

Sakmar T P

Henson G

De Clercq E

Moore J P

Article Info

Journal

Nature medicine

Abbr.

Nat Med

ISSN

1078-8956

DOI

10.1038/nm0198-072

Published

1998-01-00

Pages

72-7

Language

English

Region

United States

NLM ID

9502015

Subset

Grants

NIAID NIH HHS · AI 41420 · United States

External Links

PubMed source DOI: 10.1038/nm0198-072 View journal details

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AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor.

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