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

Article Details

Citation

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

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

Nat Med. 1998 Jan;4(1):72-7.

PubMed ID
9427609 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
C-X-C chemokine receptor type 4P61073Details
Stromal cell-derived factor 1P48061Details