EPI-X4 derivatives

**EPI-X4 derivatives** are synthetic, optimized peptide analogs derived from the endogenous 16-amino-acid fragment of human serum albumin (hSA 408-423, sequence LVRYTKKVPQVSTPTL) that acts as a specific antagonist and inverse agonist of the CXC-motif-chemokine receptor 4 (CXCR4). These derivatives, such as the 12-mer leads **EPI-X4 WSC02** (IVRWSKKVPCVS) and **EPI-X4 JM#21** (ILRWSRKLPCVS), exhibit 100- to 300-fold higher potency (nM range IC50) than native EPI-X4 (μM range), blocking CXCL12/CXCR4 signaling, HIV-1 entry using CXCR4 as co-receptor, cancer cell migration, and inflammatory leukocyte recruitment without engaging CXCR7. They demonstrate superior efficacy over AMD3100 (plerixafor) in mouse models of atopic dermatitis, eosinophilic asthma, allergic airway inflammation, and cancer, with topical administration showing therapeutic benefit; advanced variants feature N-terminal D-amino acid modifications or C-terminal amidation for >8-hour plasma stability, and albumin conjugation via disulfide or maleimide linkers enhances pharmacokinetics while preserving CXCR4 antagonism.[1][2][3][4][7][9]

Other names

WSC02WSC-02WSC 02JM#21