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The bicyclam AMD3100 story

Abstract

The discovery and development of the bicyclam AMD3100 — a chemokine receptor antagonist — has highlighted the therapeutic potential of such compounds in HIV infection, inflammatory diseases, cancer and stem-cell mobilization. Here, I describe the development process of AMD3100, which began about 15 years ago with the isolation of an impurity, and the basis for the clinical application of AMD3100 and its congeners.

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Figure 1: Polyoxometalates as potential anti-HIV agents2,3.
Figure 2
Figure 3: Mechanism of action of bicyclams: inhibiting viral entry by blocking the CXCR4 receptor.
Figure 4: Deducing the direct target of AMD3100.
Figure 5: Effect of AMD3100 on white blood cell counts.
Figure 6: The CXCR4 receptor.

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Acknowledgements

This article was conceived after the inaugural lecture of the Course on Antiviral Chemotherapy that I taught as Francqui Chair holder at the Université Catholique de Louvain (UCL), Brussels, Belgium. I wish to thank all my colleagues (see list of references) who contributed to the 'bicyclam AMD3100 story'. Special thanks are due to Christiane Callebaut for her invaluable editorial help.

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CCR5

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gp120

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SDF-1

CancerGov

Breast cancer

non-Hodgkin's lymphoma

ovarian cancer

pancreatic cancer

Online Mendelian Inheritance in Man

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De Clercq, E. The bicyclam AMD3100 story. Nat Rev Drug Discov 2, 581–587 (2003). https://doi.org/10.1038/nrd1134

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