J-113863

J-113863 is a potent and selective CCR1 antagonist with IC₅₀ values of 0.9 nM and 5.8 nM for human and mouse CCR1 receptors, respectively. J-113863 is also a potent antagonist of the human CCR3 (IC₅₀ of 0.58 nM) , but a weak antagonist of the mouse CCR3 (IC₅₀ of 460 nM). J-113863 is inactive against CCR2, CCR4 and CCR5, as well as the LTB4 or TNF-α receptors. Anti-inflammatory effect^[1][2][3]. In Vitro:Modified Vaccinia virus Ankara (MVA) but not MVA and vaccinia virus (VACV) infected MH-S cells increase the expression of the CXCR2 acting chemokine CXCL2. MH-S cells constitutively produce CCL2 and CCR1 acting chemokines CCL3, CCL5 and CCL9. Consequently, supernatants of mock treated and virus infected MH-S cells induce chemotaxis of murine promyelocyte MPRO cells and human monocytic THP-1 cells at the same level. However, supernatants of MVA infected MH-S cells significantly increase chemotaxis of the CCR2 deficient human monocytic cell line U-937. Chemotaxis of all above cell types is inhibited by J-113863^[1]. In Vivo:J-113863 (3-10 mg/kg; intraperitoneal injection; once daily; for 11 days; DBA-1 male mice) treatment improves paw inflammation and joint damage, and dramatically decreases cell infiltration into joints in arthritic mice^[2].