Introduction

CXCR4 antagonists play an important role in cancer diagnosis and therapy by primarily inhibiting metastatic spread. The present patent relates to peptides which inhibit the CXCR4 chemokine receptor.

Technical features

The chemokine receptor 4 (CXCR4), is an evolutionarily highly conserved G protein coupled receptor (GPCR) expressed on monocytes, B cells, and naive T cells. CXCR4 is activated by a specific ligand CXCL12 and the activation of the axis controls cell growth, invasion and migration. In cancer CXCR4 is overexpressed in more than 23 human cancers where promotes metastases. In addition the interruption of the CXCR4–CXCL12 axis modifies tumor microenvironment (TME) favoring access of immune active cells to the TME. Targeting tumoral and TME CXCR4 with specific probe may allow diagnosis and follow of CXCR4 expressing tumors. Unique CXCR4 antagonist approved for therapy is a small molecule, AMD3100, indicated to promote hematopoietic precursor mobilization.

 

Possible Applications

• Cancer Therapy ( tumor growth inhibition, anti-metastatic, immunemodulation);
• Cancer Diagnosis (PET-imaging of CXCR4 expressing lesion, PET-imaging of tumor microenvironment);
• Rare Disease: WHIM syndrome, Waldenström macroglobulinemia.

Advantages

• Nanomolar efficacy;
• Rational Design amenable to functional modifications;
• Targeting specific cancer stem cell and tumor stromal populations.