Definition

The sodium salt form of ladarixin, an orally bioavailable, small molecule, dual inhibitor of C-X-C motif chemokine receptors 1 (CXCR1) and 2 (CXCR2), with potential anti-inflammatory and antineoplastic activities. Upon oral administration, ladarixin selectively targets and allosterically binds to CXCR 1 and 2, thereby preventing CXCR1 and CXCR2 activation by their ligand and pro-inflammatory chemokine interleukin 8 (IL-8 or CXCL8). This inhibits CXCR1/2-mediated signaling, which inhibits inflammatory processes, reduces both the recruitment and migration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and neutrophils in the tumor microenvironment (TME), and abrogates the immunosuppressive-induced nature of the TME. This allows effector cells, such as natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), to kill and eliminate cancer cells, and inhibits tumor cell migration, metastasis, angiogenesis and tumor cell proliferation. CXCR1 and 2, G protein-coupled receptor proteins located on myeloid cells and certain tumor cells, play key roles in the immunosuppressive nature of the TME, tumor metastasis, resistance to chemotherapeutic agents and myeloid cell suppression. They also play a key role in inflammation and their expression is elevated in several inflammatory-driven diseases.