| Description | 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. J-113863 is a potent and selective CCR1 (CD18) antagonist with IC50 values of 0.9 nM and 5.8 nM for human and mouse CCR1 receptors, respectively. |
| In vitro | The chemotaxis of the following cells were inhibited by J-113863. 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. |
| In vivo | J-113863 treatment improves paw inflammation and joint damage, and dramatically decreases cell infiltration into joints in arthritic mice. |
| Target activity | CCR1:5.8 nM (IC50, Mouse CCR1), CCR1:0.9 nM (IC50, Human CCR1), CCR3:460 nM (IC50, Mouse CCR3), CCR3:0.58 nM (IC50, Human CCR3) |
| molecular weight | 655.44 |
| Molecular formula | C30H37Cl2IN2O2 |
| CAS | 353791-85-2 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 6.56 mg/mL (10 mM) |
| References | 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. |