The bicyclam
AMD3100 (originally called
JM3100), in which the two
cyclam rings are tethered by an aromatic bridge, emanated from
JM2763, where the two
cyclam moieties are tethered by an aliphatic linker -
JM2763 in turn originated from JM1657, where the
cyclam rings are directly linked to one another via a C-C bridge, and which was identified as an impurity, showing anti-HIV activity, in a commercial
cyclam preparation.
AMD3100 proved very effective against HIV-1 and HIV-2, inhibiting virus replication within the nM range, without toxicity for the host cells at concentrations that were > 100,000-fold higher than those required to inhibit HIV replication. The anti-HIV activity of
AMD3100 appeared to be confined to the T-lymphotropic (X4) HIV strains, i.e. those strains that use the
CXCR4 receptor to enter their target cells, and
AMD3100 as of today still stands as one of the most potent and selective CXCR4 antagonists ever discovered. Hence,
AMD3100 was found to interfere with a number of (patho)physiological processes which depend on the interaction of CXCR4 with its natural
ligand, stromal derived factor (SDF-1) and which play an important role in rheumatoid, allergic and malignant diseases.
AMD3100 has been shown to mobilize CD34+ stem cells from the bone marrow into the bloodstream and has also been shown to augment migration of bone marrow-derived endothelial progenitor cells into sites of neovascularization after
myocardial infarction. Currently,
AMD3100 is actively pursued as a stem cell mobilizer for
transplantation in patients with
multiple myeloma and
non-Hodgkin's lymphoma.