AMD 3465 (hexahydrobromide)

AMD 3465 hexahydrobromide (GENZ-644494 hexahydrobromide) is a potent antagonist of CXCR4, inhibits binding of 12G5 mAb and CXCL12^AF647 to CXCR4, with IC₅₀s of 0.75 nM and 18 nM in SupT1 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. IC50 & Target: IC50: 0.75 nM (12G5 mAb-CXCR4), 18 nM (CXCL12^AF647-CXCR4), 1-10 nM (X4 HIV)^[1] In Vitro: AMD 3465 hexahydrobromide is a potent antagonist of CXCR4, inhibits binding of 12G5 mAb and CXCL12^AF647 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]. In Vivo: AMD 3465 (2.5 mg/kg/d, s.c. for 5 weeks) significantly blocks the growth of U87 GBM and Daoy xenografts^[2].