In vitro study | AMD3465 blocks the binding of CXCL12 in SupT1 cells with an IC50 of 18 nM. AMD3465 also inhibits cxcl12-induced calcium signaling with an IC50 of 17 nM and inhibits MAPK phosphorylation. However, AMD3465 was unable to block the intracellular calcium flux induced by the CCR5 ligands RANTES, LD78β and MIP-1β in U87.CD4.CCR5 cells. AMD3465 inhibits cxcl12-induced chemotaxis in human T lymphoid SupT1 cells and prevents chemokine-induced CXCR4 internalization in ud7.cd4 cells. In addition, the study showed that AMD3465 can inhibit the activity of X4 HIV-1 strain IIIB, NL4.3, RF and HE, IC50 range 6-12 nM. AMD3465 inhibited ROD and EHO of HIV-2 strains with IC50 of 12.3 nM. AMD3465 inhibited the binding of SDF-1α ligand at K I of 41.7 nM in CCRF-CEM cell line. Inhibition of the CXCR4 signaling pathway by AMD3465 was achieved by inhibiting SDF-1α-stimulated calcium flux and GTP binding with IC50 of 12.07 nM and 10.38 nM, respectively. In addition, AMD3465 can inhibit the physiological response mediated by CXCR4, cell chemotaxis, IC50 is 8.7 nM. In addition, AMD3465 on MIP1α, MCP-1, TARC, RANTES, MIP-3β and IP10 mediated calcium flow, CCR1, The corresponding ligands of CCR2b, CCR4, CCR5, CCR7 and CXCR3, as well as the binding of LTB 4 to BLT1, are not effective, thus indicating that AMD3465 is a selective inhibitor of CXCR4 and not against other chemokines. An independent study showed that AMD3465 could inhibit SDF-1 of CXCR4 internalization mediated in GFP-conjugated CXCR4 expressing cells without receptor internalization when incubated with cells alone. |