AMD 3465 also potently inhibits the replication of X4 HIV strains (IC50: 1-10 nM). However, it has no effect on CCR5-using (R5) viruses. AMD 3465 (GENZ-644494) is a potent antagonist of CXCR4, inhibits binding of 12G5 mAb and CXCL12AF647 to CXCR4, with IC50s of 0.75 nM and 18 nM in SupT1 cells.

X4 HIV-1 (HE):9.8 nM （in MT-4 cells), HIV-2 (ROD):12.3 nM （in MT-4 cells), X4 HIV-1 (IIIB):12.3 nM （in MT-4 cells), X4 HIV-1 (RF):7.4 nM （in MT-4 cells), 12G5 mAb-CXCR4:0.75 nM （in SupT1 cells), CXCL12 (AF647)-CXCR4:18 nM （in SupT1 cells), X4 HIV-1 (NL4.3):6.1 nM （in MT-4 cells), X4 HIV-1 (NL4.3AMD3100):2822 nM （in MT-4 cells), HIV-2 (EHO):12.3 nM （in MT-4 cells)

AMD 3465 is a potent CXCR4 antagonist, inhibiting the binding of 12G5 mAb and CXCL12AF647 to CXCR4 with IC50 values of 0.75 nM and 18 nM in SupT1 cells. It is cytotoxic to X4 HIV-1 strains IIIB, NL4.3, RF, and HE with IC50 values of 6-12 nM, and it inhibits CXCL-12-induced growth in U87 and Daoy cells. AMD 3465 treatment stimulates Erk1/2 phosphorylation in U87 and Daoy cells[2], and at 50 nM, it completely blocks CXCL12-induced calcium mobilization (IC50: 17 nM), while showing no effect on CCR5 ligand-induced calcium fluxes in U87.CD4.CCR5 cells. It also potently inhibits X4 HIV strains (IC50: 1-10 nM), but has no effect on CCR5-using (R5) viruses, with an IC50 of 12.3 nM for suppressing HIV-2 strains ROD and EHO[1].

AMD 3465, administered subcutaneously at a dosage of 2.5 mg/kg/day for five weeks, significantly inhibits the growth of U87 glioblastoma multiforme (GBM) and Daoy xenograft tumors.