Background
Molecular pharmacology of AMD3100 in blocking CXCR4
Clinical applications
HIV entry inhibitor
Stem cell mobilization
Application of AMD3100 in leukemia
Treatment of acute lymphoblastic leukemia
Treatment of chronic lymphocytic leukemia
Treatment of acute myelogenous leukemia
The approach of combinational use of AMD3100 with MER kinase inhibitor to improve anti-tumor drug efficacy in the context of acute myelogenous leukemia
Treatment of chronic myeloid leukemia
Treatment of other type of leukemia
Application of AMD3100 in solid tumors
Use of [64Cu]AMD3100 in molecular imaging of CXCR4 expressed tumors
Conclusion
CXCR4 antagonist | Source | Target profile | Advantage | Citation | |
---|---|---|---|---|---|
Primary targets | Activity | ||||
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 | |
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 | |
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] |