EPI-X4 is a peptide antagonist of CXCR4 with therapeutic prospects for cancer and inflammatory disorders

Abstract

In a deregulated state, the CXCR4/CXCL12 signaling pathway plays a significant role in the development of cancer and inflammatory disorders. Currently, plerixafor (AMD3100) is the only approved CXCR4 antagonist used to mobilize hematopoietic stem cells into the peripheral blood for transplantation therapy. There is a need to develop new compounds to treat cancer by inhibiting the CXCR4/CXCL12 axis. This review focuses on the role CXCR4/CXCL12 axis in cancer development and its inhibitors identified thus far. One interesting compound is the endogenous peptide inhibitor for CXCR4 (EPI-X4), recently discovered in the hemofiltrate of dialysis patients. It was traced back to human serum albumin, from where it was generated by the proteolytic activity of cathepsins E and D. Based on its implications for cancer therapy, this review describes its recent evaluations, which include sequence optimization, in vivo efficacy, toxicity, and bioavailability studies.