The CC-type chemokine receptor 1 (CCR1) is a chemokine receptor of significant importance in human health. CCR1 is a protein that in humans is encoded by the CCR1 gene. Moreover, CCR1 exhibits significant constitutive activity leading to a variety of cellular responses. The chemokine receptor CCR1 is a member of a receptor superfamily that binds multiple CC-chemokines. Of these, the most representatives are CCL3/macrophage inflammatory protein-1α (MIP-1α) and CCL5. Furthermore, CCR1 is a potential target for the treatment of rheumatoid arthritis. Several nonpeptide CCR1 receptor antagonists that show high affinity for human CCR1 receptors

J-113863 is a non-peptide antagonist of the mouse receptor. In particular, J-113863 is a CCR1 antagonist. Importantly, J-113863 has IC50 values of 0.9 and 5.8 nM for human and mouse CCR1 receptors, respectively.

Up to now, researchers used J-113863 to explore the impact of CCR1 blockade in experimental arthritis and the underlying mechanisms. Treatment of THP-1 cells with J-113863 reduces background levels of THP-1 cell chemotaxis towards supernatants from mock-infected cells and medium controls. J-113863 does not inhibit mouse TNFα in vitro but induces a trend towards increased TNFα release in cells from synovial membranes of rheumatoid arthritis patients.

In vivo, researchers tested J-113863 in collagen-induced arthritis (CIA). Treatment of arthritic mice with J-113863 improves paw inflammation and joint damage and dramatically decreases cell infiltration into joints. J-113863 does not inhibit IL-2 or DTH but reduces plasma TNFα levels in LPS-treated mice. Surprisingly, J-113863 decreases TNFα also in CCR1 null mice.

All in all,  J-113863 is a non-peptide antagonist of the mouse receptor for the blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo.

Amat M, et al.  Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo. Br J Pharmacol. 2006 Nov;149(6):666-75.