Table 1 Comparison of AMD3100 with other CXCR4 antagonists on the development

AMD3100

Compound

TM-IV (Asp¹⁷¹), TM-VI (Asp²⁶²), and TM-VII (Glu²⁸⁸)

IC50 = 2–20 nM

The only approved CXCR4 antagonist; no species specific, thus studies of AMD3100 in mouse, canine, monkey, and cell lines have translated into human clinical studies quickly

De Clercq [2, 3, 17, 18]; Hatse et al. [16]

EPI-X4

Endogenous peptide

The positively charged face of the ring of EPI-X4 interacts with the negatively charged extracellular face of CXCR4

IC50 = 8.6 ± 3.1 µM

Endogenous antagonist; no cytotoxity

Zirafi et al. [74]

KRH-3955

Compound

Binding sites of KRH-3955 are located in a region composed of all three extracellular loop (ECLs) of CXCR4

IC50 = 0.61 nM

Administered orally with much more potent anti-HIV-1 activity than AMD3100 and KRH-1636

Murakami et al. [75]

POL5551

Compound

Similar to plerixafor, POL5551 bound to the extracellular loops but not to the N-terminal moiety recognized by 1D9

IC50 of 12G5 binding at 1 h ≤2.5 nM

POL5551 is a potent antagonist of surface CXCR4 in pre-B and T cell ALL cell lines

Karpova et al. [76]; Sison et al. [77]

LY2510924

Compound

LY2510924 occupied a binding pocket and possessed ligand–receptor interactions with CXCR4 residues such as Asp187, Arg188, Gln200, His113, and Tyr190

IC50 = 0.079 nM

Phase II clinical studies for cancer

Peng et al. [78]