Biological characterization of a synthetic CXCR4 antagonist with dual antimetastasis and antiangiogenesis activities

Metastasis and angiogenesis are two of the major obstacles that hinder the successful treatment of human cancers. C-X-C chemokine receptor type 4 (CXCR4), an important regulator of cancer metastasis and angiogenesis, is predominantly expressed in many metastatic cancers. We evaluated the antimetastasis and antiangiogenesis effects DV1, our recently developed potent CXCR4 antagonist, both in vitro and in vivo. DV1, a mimetic of the essential molecular moieties of a naturally existing CXCR4 ligand, consists of all D amino acids. At low nanomolar concentrations, DV1 strongly inhibited the in vitro tubule formation activity of HUVECs, the transwell migration of CXCR4+ cancer cells, and in vivo cancer metastasis and growth. These results support the continued development of this compound as a potential CXCR4 antagonist and a therapeutic drug that targets angiogenesis and cancer metastasis.