N-[[4-(1,4,8,11-四氮杂环十四烷-1-基甲基)苯基]甲基]-2-吡啶甲胺

N-[[4-(1,4,8,11-四氮杂环十四烷-1-基甲基)苯基]甲基]-2-吡啶甲胺化学性质

N-[[4-(1,4,8,11-四氮杂环十四烷-1-基甲基)苯基]甲基]-2-吡啶甲胺性质、用途与生产工艺

生物活性 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。

靶点

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)

体外研究

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.
体内研究

AMD 3465 (2.5 mg/kg/d, s.c. for 5 weeks) significantly blocks the growth of U87 GBM and Daoy xenografts.

N-[[4-(1,4,8,11-四氮杂环十四烷-1-基甲基)苯基]甲基]-2-吡啶甲胺上下游产品信息

上游原料

下游产品

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