Definition

An orally bioavailable non-competitive and selective antagonist of the fractalkine (C-X3-C motif chemokine 1; chemokine ligand 1; CX3CL1; small-inducible cytokine D1) receptor (CX3C chemokine receptor 1; CX3CR1; chemokine, CX3C motif, receptor 1), with potential anti-inflammatory, immunomodulatory and antineoplastic activities. Upon oral administration, fractalkine receptor antagonist KAND567 specifically and allosterically binds to and blocks CX3CR1, thereby preventing the binding of fractalkine to its receptor and preventing the activity of CX3CR1. This prevents CX3CR1-mediated signaling, prevents the recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and monocytes into tissues and vital organs and inhibits the exaggerated inflammatory response and the associated tissue damage caused by hyperinflammation. KAND567 also binds to and blocks CX3CR1 on cancer cells, thereby inhibiting proliferation of CX3CR1-expressing tumor cells. In addition, blocking CX3CR1 may suppress DNA repair processes of damaged DNA which prevents cancer cell survival following treatment with DNA damaging agents. Fractalkine, an immunomodulating factor and chemokine, controls the function of certain immune and cancer cells. Fractalkine and its receptor CX3CR1 are elevated in and play key roles in several cancers, inflammatory diseases and heart disease.