KAND567 (AZD8797) is a potent, selective and orally available C-X3-C motif chemokine receptor 1 (CX3CR1, fractalkine receptor) antagonist with binding Ki of 3.9 nM (human CX3CR1), 720-fold selectivity over CXCR2.
KAND567 shows 246-fold selectivity versus hCCR1 and 187-fold versus hCCR2 and no significant antagonism of the CCR4, CCR5, CCR6, CXCR3, and CXCR5 receptor.
KAND567 also does not show significant interactions with the majority of the targets in a broad screen with 65 different receptors, enzymes, or ion channels.
KAND567 exhibits fractalkine stimulated GTPγS binding in the low nanomolar range, potent inhibition of human peripheral blood monocyte adhesion to a FKN-coated surface, and potent inhibition of soluble FKN-induced monocyte migration.
KAND567 inhibits FKN-induced actin polymerization in monocytes from human and rat blood.
KAND567 reverses clinical symptoms, reduces spinal cord neuroinflammation and demyelination in the rat experimental autoimmune encephalomyelitis (EAE) disease model of MS.