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

Nature Medicine volume 4, pages 72–77 (1998)Cite this article

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-1α, 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.

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Authors and Affiliations

  1. The Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, New York, 10016, USA

    George A. Donzella & John P. Moore

  2. Rega Institute for Medical Research, Katholieke Universiteit, Minderbroederstraat 10, B-3000, Leuven, Belgium

    Dominique Schols, José A. Esté & Erik DeClercq

  3. Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York, 10021, USA

    Steven W. Lin & Thomas P. Sakmar

  4. Progenics Pharmaceuticals, 777 Saw Mill River Road, Tarrytown, New York, 10591, USA

    Kirsten A. Nagashima, Paul J. Maddon & Graham P. Allaway

  5. AnorMED, No. 100-20353 64th Avenue, Langley, British Columbia, Canada, V2Y 1N5

    Geoffrey Henson

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Donzella, G., Schols, D., Lin, S. et al. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat Med 4, 72–77 (1998). https://doi.org/10.1038/nm0198-072

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