Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes including chronic inflammatory diseases and cancer. Thus, the chemokine receptor CXCR4 is a promising target for the therapy of inflammatory disorders and cancers. A natural fragment of serum albumin, named EPI-X4, has previous been identified as endogenous peptide antagonist and inverse agonist of CXCR4. EPI-X4 analogs with increased anti-CXCR4 activity and plasma stability have been developed. This section must be of suitable quality to enable direct publication by the Agency. This report should address a wide audience, including the general public. It shall cover the results and the conclusion of the project as well as its socioeconomic impact, if any.In the funded project, optimized EPI-X4 analogs were evaluated for their ability to prevent inflammatory reactions and tumor growth in vitro and in vivo. We performed PK studies in mice and identified a lead analog that is currently being analyzed in mouse xenograft models of colon carcinoma and osteosarcoma. The optimized analog EPI-X4 JM#21 was also analyzed as topically applied compounds in mouse models of atopic dermatitis and asthma. The CXCR4 antagonizing peptide efficiently reduced inflammation of the skin and infiltration of immune cells into the lung without causing side effects. Thus, further preclinical and clinical development of EPI-X4 to prevent and treat inflammatory diseases is highly warranted.
