AMD3100 was found to inhibit HIV-1 and HIV-2 within the 1-10nM concentration range while not being toxic to the host cells at concentrations up to 500 microM, thus achieving a selectivity index of approximately 100,000. The target of action was initially thought to be the viral envelope
glycoprotein gp120. It appeared only to be the indirect target. The direct target of action turned out to be the co-
receptor CXCR4 used by T-lymphotropic HIV strains (now referred to as X4 strains) to enter the cells. Initial (phase I) clinical trials undertaken with
AMD3100, as a prelude to its development as a candidate
anti-HIV drug for the treatment of
AIDS, showed an unexpected side effect: an increase in the white blood cell counts. Apparently,
AMD3100 specifically increased CD34+ hematopoietic stem cell counts in the peripheral blood. Stromal derived factor 1 (SDF-1), through its interaction with CXCR4, retains the stem cells in the bone marrow (a process referred to as "homing"), and
AMD3100 specifically antagonizes this interaction.
AMD3100 in combination with
granulocyte colony-stimulating factor (
G-CSF) resulted in the collection of more progenitor cells than
G-CSF alone. At present, the major indication for clinical use of
AMD3100 (
Mozobil) is the mobilization of hematopoietic stem cells from the bone marrow into the circulating blood for
transplantation in patients with
hematological malignancies such as
non-Hodgkin's lymphoma or
multiple myeloma.