AMD 3465 hexahydrobromide (GENZ-644494 (hexahydrobromide)) is a CXCR4 receptor antagonist with potential anticancer and anti-HIV activity.

X4 HIV-1 (HE):9.8 nM (IC50, in MT-4 cells), CXCL12 (AF647)-CXCR4:18 nM (IC50, in SupT1 cells), 12G5 mAb-CXCR4:0.75 nM (IC50, in SupT1 cells), X4 HIV-1 (NL4.3):6.1 nM (IC50, in MT-4 cells), HIV-2 (EHO):12.3 nM (IC50, in MT-4 cells), HIV-2 (ROD):12.3 nM (IC50, in MT-4 cells), X4 HIV-1 (IIIB):12.3 nM (IC50, in MT-4 cells), X4 HIV-1 (NL4.3AMD3100):2822 nM (IC50, in MT-4 cells), X4 HIV-1 (RF):7.4 nM (IC50, in MT-4 cells)

AMD 3465 hexahydrobromide inhibits binding of 12G5 mAb and CXCL12AF647 to CXCR4, with IC50s of 0.75 nM and 18 nM in SupT1 cells.?AMD 3465 (50 nM) totally blocks CXCL12-induced calcium mobilization, with an IC50 of 17 nM, but shows no effect on the intracellular calcium fluxes elicited by the CCR5 ligands RANTES, LD78β and MIP-1β in U87.CD4.CCR5 cells.?AMD 3465 also potently inhibits the replication of X4 HIV strains (IC50: 1-10 nM), but has no effect on CCR5-using (R5) viruses.?AMD3465 is cytotoxic to the X4 HIV-1 strains IIIB, NL4.3, RF and HE with an IC50 ranging from 6 to 12 nM.?The IC50 for suppression of the HIV-2 strains ROD and EHO is 12.3 nM[1].?AMD 3465 inhibits CXCL-12-induced growth in U87 and Daoy cells.?AMD 3465 treatment stimulates the phosphorylation of Erk1/2 in U87 and Daoy cells[2].

Administering 2.5 mg/kg/d of AMD 3465 subcutaneously for five weeks significantly inhibits the growth of U87 glioblastoma multiforme (GBM) and Daoy medulloblastoma xenografts.