AMD3465 hexahydrobromide

Category	Human immunodeficiency Virus (HIV)
CAS	185991-07-5
Description	AMD 3465 is a potent and selective antagonist of CXCR4, 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. MD3465 was even 10-fold more effective as a CXCR4 antagonist, while showing no interaction whatsoever with CCR5. AMD3465 has the potential to mobilize hematopoietic stem cells.

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Product Information

Synonyms	AMD3465; GENZ-644494 hexahydrobromide
Molecular Weight	896.07
Molecular Formula	C24H38N6·6HBr
Canonical SMILES	C1(CNCC2=CC=C(CN3CCNCCCNCCNCCC3)C=C2)=NC=CC=C1.[6HBr]
InChI	InChI=1S/C24H38N6/c1-2-13-29-24(5-1)20-28-19-22-6-8-23(9-7-22)21-30-17-4-12-26-15-14-25-10-3-11-27-16-18-30/h1-2,5-9,13,25-28H,3-4,10-12,14-21H2
InChIKey	CWJJHESJXJQCJA-UHFFFAOYSA-N
Boiling Point	571.3±50.0 °C at 760 mmHg
Flash Point	299.3±30.1 °C
Purity	≥95%
Density	1.0±0.1 g/cm3
Solubility	Soluble to 50 mM in water and to 25 mM in DMSO.
Appearance	Crystalline Solid
Storage	Powder: -20°C: 3 years 4°C: 2 years In solvent: -80°C: 6 months -20°C: 1 month
Animal Admin	Two weeks after tumor cell implantation, cohorts of mice with approximately equivalent tumor bioluminescence are divided into equal control and treatment groups. Animals in AMD 3465 experiments receive s.c. osmotic pumps loaded with 10 mg/mL AMD 3465 in sterile PBS or PBS alone. Mice are imaged at least twice after implantation of cells to identify those with equivalent tumor growth rates.
Complexity	413
Exact Mass	410.315796
Index Of Refraction	1.533
In Vitro	AMD 3465 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. 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. 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.
In Vivo	AMD 3465 (2.5 mg/kg/d, s.c. for 5 weeks) significantly blocks the growth of U87 GBM and Daoy xenografts.
Target	2G5 mAb-CXCR4:0.75 nM (IC50, in SupT1 cells) CXCL12AF647-CXCR4:18 nM (IC50, in SupT1 cells) X4 HIV-1 (IIIB):12.3 nM (IC50, in MT-4 cells) X4 HIV-1 (NL4.3):6.1 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) X4 HIV-1 (HE):9.8 nM (IC50, in MT-4 cells) HIV-2 (ROD):12.3 nM (IC50, in MT-4 cells) HIV-2 (EHO):12.3 nM (IC50, in MT-4 cells)
Vapor Pressure	0.0±1.6 mmHg at 25°C