Definition

A peptide-drug conjugate (PDC) of paclitaxel with an inhibitor of CXC chemokine receptor 4 (CXCR4), with potential antineoplastic activity. Upon administration of paclitaxel-conjugated CXCR4 peptide antagonist MB1707, the CXCR4 inhibitor moiety binds to the chemokine receptor CXCR4 expressed on tumor cells, thereby preventing CXCR4 binding to its ligand, stromal derived factor-1 (SDF-1), and subsequent receptor activation. This may result in decreased tumor cell proliferation and migration. In addition, paclitaxel binds to tubulin inside CXCR4-expressing tumor cells and inhibits the disassembly-assembly dynamics of microtubules, resulting in cell cycle arrest and cell death. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types. By targeting CXCR4-expressing tumor cells specifically, paclitaxel’s efficacy is increased while minimizing systemic toxiciy.