AMD3100 was originally discovered as an
anti-HIV agent effective in inhibiting the replication of HIV in vitro at nanomolar concentrations. We found it to be a potent and selective antagonist of CXCR4, the receptor for the
chemokine SDF-1 (now called CXCL12).
AMD3100 was then developed, and marketed, as a stem cell mobilizer, and renamed
plerixafor (Mozobil™). The path to the discovery of Mozobil™ as a stem cell mobilizer was described in Biochem. Pharmacol. 77: 1655-1664 (2009). Here I review the recent advances that have consolidated the role of
plerixafor in mobilizing hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) from the bone marrow into the blood circulation.
Plerixafor acts synergistically with
granulocyte colony-stimulating factor (
G-CSF), and its usefulness has been proven particularly for the mobilization of HSCs and HPCs for autologous
stem cell transplantation in patients with
non-Hodgkin's lymphoma (NHL) or
multiple myeloma (MM).
Plerixafor also has great potential for the treatment of
hematological malignancies other than NHL and MM, and non-
hematological malignancies, and, eventually, several other diseases depending on the CXCL12-CXCR4 interaction. Various
AMD3100 analogs have been described (i.e.
AMD11070,
AMD3465,
KRH-3955, T-140, and 4F-benzoyl-
TN14003), primarily as potential
anti-HIV agents. They are all strong CXCR4 antagonists. Their role in
stem cell mobilization remains to be assessed.