J 113863

J-113863 is a potentand 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 has no active against CCR2, CCR4 and CCR5, as well as the LTB4 or TNF-α receptors. Anti-inflammatory effect[1][2][3].

Signaling Pathways >> GPCR/G Protein >> CCR

Signaling Pathways >> Immunology/Inflammation >> CCR

Research Areas >> Inflammation/Immunology

CCR1:0.9 nM (IC50, Human CCR1)

CCR1:5.8 nM (IC50, Mouse CCR1)

CCR3:0.58 nM (IC50, Human CCR3)

CCR3:460 nM (IC50, Mouse CCR3)

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].

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]. Animal Model: DBA-1 male mice (10-12 weeks) induced with Collagen[2] Dosage: 3 mg/kg, 10 mg/kg Administration: Intraperitoneal injection; once daily; for 11 days Result: Improved paw inflammation and joint damage, and dramatically decreased cell infiltration into joints.

[1]. Lehmann MH, et al. Modified Vaccinia virus Ankara but not vaccinia virus induces chemokine expression in cells of the monocyte/macrophage lineage. Virol J. 2015 Feb 12;12:21.

[2]. 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.

[3]. Naya A, et al. Design, synthesis, and discovery of a novel CCR1 antagonist. J Med Chem. 2001 Apr 26;44(9):1429-35.