AMD 3465 (GENZ-644494) 是一种有效的 CXCR4 拮抗剂，在 SupT1 细胞中，能够抑制 12G5 mAb，CXCL12AF647 与 CXCR4 结合，IC50 值分别为 0.75 nM 和 18 nM；AMD 3465 同时可有效抑制 X4 HIV 的复制 (IC50，1-10 nM)，但对 R5 HIV 病毒无作用。
|
12G5 mAb-CXCR4
0.75 nM (IC
50
, in SupT1 cells)
|
CXCL12
AF647
-CXCR4
18 nM (IC
50
, in SupT1 cells)
|
X4 HIV-1 (III
B
)
12.3 nM (IC
50
, in MT-4 cells)
|
X4 HIV-1 (NL4.3)
6.1 nM (IC
50
, in MT-4 cells)
|
X4 HIV-1 (NL4.3
AMD3100
)
2822 nM (IC
50
, in MT-4 cells)
|
X4 HIV-1 (RF)
7.4 nM (IC
50
, in MT-4 cells)
|
X4 HIV-1 (HE)
9.8 nM (IC
50
, in MT-4 cells)
|
HIV-2 (ROD)
12.3 nM (IC
50
, in MT-4 cells)
|
HIV-2 (EHO)
12.3 nM (IC
50
, in MT-4 cells)
|
AMD 3465 is a potent antagonist of CXCR4, inhibits binding of 12G5 mAb and CXCL12
AF647
to CXCR4, with IC
50
s of 0.75 nM and 18 nM in SupT1 cells. AMD 3465 (50 nM) totally blocks CXCL12-induced calcium mobilization, with an IC
50
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 (IC
50
: 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 IC
50
ranging from 6 to 12 nM. The IC
50
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.