Bicyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor fusin/CXCR-4

Antiviral Res. 1997 Aug;35(3):147-56. doi: 10.1016/s0166-3542(97)00025-9.


Bicyclams are a novel class of antiviral compounds which are highly potent and selective inhibitors of the replication of HIV-1 and HIV-2. The prototype compound, AMD3100, has an IC50 of 1-10 ng/ml, which is a least 100,000 fold lower than the cytotoxic concentration. AMD3100 does not inhibit virus binding to the CD4 receptor and based on time-of-addition experiments, has been assumed to interact with the HIV fusion-uncoating process. Resistance of HIV-1 strains to AMD3100 is associated with the accumulation of several mutations in the viral envelope glycoprotein gp120. Here, we demonstrate that AMD3100 interacts with fusin (CXCR-4), the coreceptor used by T-tropic viruses to infect the target cells. The replication of NL4-3 wild type virus and NL4-3 dextran sulfate-resistant virus was inhibited by the CXC-chemokine, stromal cell-derived factor 1 (SDF-1), the natural ligand for CXCR-4. In contrast, the replication of the HIV-1 NL4-3 AMD3100-resistant virus was no longer inhibited by SDF-1. The bicyclams are the first low-molecular-weight anti-HIV agents shown to interact with the coreceptor for T-tropic viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Benzylamines
  • Cell Line
  • Cells, Cultured
  • Cyclams
  • GTP-Binding Proteins / drug effects
  • GTP-Binding Proteins / metabolism
  • HIV / drug effects*
  • HIV / metabolism*
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Membrane Proteins / drug effects*
  • Receptors, CXCR4
  • Receptors, HIV / drug effects*
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / metabolism
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Membrane Proteins
  • Receptors, CXCR4
  • Receptors, HIV
  • GTP-Binding Proteins
  • plerixafor