AMD3451 is a specific, dual CXCR5/CXCR4 antagonist with antiviral activity against a wide variety of HIV-1 and HIV-2 (IC50=1.2 to 26.5 uM) in vitro.AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains if HIV-1 and HIV-2 in various T-cell lines, CCR5- or CXCR4-transfected cells, PBMCs, and monocytes/macrophages.AMD3451 inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC50, 1.8 to 7.3 uM), AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage.AMD3451 dose-dependently inhibited the intracellular Ca2+ signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca2+ flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells.AMD3451 did not interfere with chemokine-induced Ca2+ signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca2+ signaling by itself at 400 uM.AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells.AMD3451 does not inhibit the binding of CXCR4- or CCR5-specific MAbs.
