C-X-C chemokine receptor type 4 is a receptor for the stromal cell-derived factor-1 which is designated as chemokine ligand 12 (CXCL12). It is involved in cell progression, hematopoiesis, cancer, HIV entry, and rheumatoid arthritis. AMD 3465 blocks the cell surface binding of CXCL12 with an IC50 value of 18 nM. It inhibits CXCL12-induced calcium mobilization (IC50 = 4 nM) and at 6,250 nM completely blocks CXCL12-induced chemotaxis of SupT1 cells. AMD 3465 is active against various HIV strains with IC50 values ranging from 6 to 12 nM. It dose dependently inhibits eosinophil recruitment during type-2 granuloma formation and interferes with primary and secondary T-cell activation events in lymphoid tissue. At 50 μg/day, AMD 3465 blocks tumor growth and prevents CXCL12-induced cAMP suppression in xenograft models of medulloblastoma and glioblastoma.
