Plerixafor (hydrochloride hydrate)

The α-chemokine receptor, CXCR4, on CD4⁺ T-cells is used by CXCR4-selective HIV forms as a gateway for T-cell infection. In mammalian cell signaling, CXCR4 activation promotes the homing of hematopoietic stem cells, chemotaxis and quiescence of lymphocytes, and growth and metastasis of certain cancer cell types. Plerixafor is a partial antagonist of chemokine receptor 4 (CXCR4) with IC₅₀ values ranging from 0.02 to 0.13 µg/ml for inhibiting calcium flux in peripheral blood mononuclear cells (PBMCs), various types of T cells, and mouse lymphocytic leukemia cells.¹ It is selective for CXCR4 over CXCR1-3 and CXCR5-9 (IC₅₀s = >25 µg/ml). Plerixafor decreases infectious virus content in the supernatant of Jurkat cells chronically infected with HIV-1(III_B) (EC₅₀ = ~0.02 µg/ml).² It rapidly mobilizes murine and human hematopoietic stem and murine long-term repopulating cells for transplantation alone and, with a synergistic effect, when used in combination with G-CSF.³ Plerixafor also increases T cell trafficking in mouse blood, spleen, and central nervous system.^4,5 Plerixafor (1.25 mg/kg twice per day) decreases the number of 4T1 murine mammary carcinoma cells in the lung in a mouse model of lung metastasis.⁶

1.Hatse, S., Princen, K., Bridger, G., et al.Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4FEBS Lett.527(1-3)255-262(2002) 2.De Clercq, E., Yamamoto, N., Pauwels, R., et al.Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100Antimicrob. Agents Chemother.38(4)668-674(1994) 3.Hess, D.A., Bonde, J., Craft, T.C., et al.Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factorBiol. Blood Marrow Transplant13(4)398-411(2007) 4.Bernardini, G., SciumÈ, G., Bosisio, D., et al.CCL3 and CXCL12 regulate trafficking of mouse bone marrow NK cell subsetsBlood111(7)3626-3634(2008) 5.McCandless, E.E., Zhang, B., Diamond, M.S., et al.CXCR4 antagonism increases T cell trafficking in the central nervous system and improves survival from west nile virus encephalitisProc. Natl. Acad. Sci. U.S.A.105(32)11270-11275(2008) 6.Smith, M.C., Luker, K.E., Garbow, J.R., et al.CXCR4 regulates growth of both primary and metastatic breast cancerCancer Res.64(23)8604-8612(2004)