J-113863 (J113863) is a novel and potent CCR1 (CD18) antagonist with anti-inflammatory. It inhibits CCR1 with with IC50 of 0.9 nM and 5.8 nM for human and mouse CCR1 receptors, respectively.
Physicochemical Properties
| Molecular Formula | C₃₀H₃₇CL₂IN₂O₂ |
| Molecular Weight | 655.44 |
| Exact Mass | 654.128 |
| CAS # | 353791-85-2 |
| PubChem CID | 6918496 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 4.98 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 37 |
| Complexity | 755 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CC[N+]1(CCC(CC1)NC(=O)C2C3=C(C=CC(=C3)Cl)OC4=C2C=C(C=C4)Cl)C/C/5=C/CCCCCC5.[I-] |
| InChi Key | FOAFBMYSXIGAOX-LQGGPMKRSA-N |
| InChi Code | InChI=1S/C30H36Cl2N2O2.HI/c1-2-34(20-21-8-6-4-3-5-7-9-21)16-14-24(15-17-34)33-30(35)29-25-18-22(31)10-12-27(25)36-28-13-11-23(32)19-26(28)29;/h8,10-13,18-19,24,29H,2-7,9,14-17,20H2,1H3;1H/b21-8+; |
| Chemical Name | 2,7-dichloro-N-[1-[[(1E)-cycloocten-1-yl]methyl]-1-ethylpiperidin-1-ium-4-yl]-9H-xanthene-9-carboxamide;iodide |
| Synonyms | J113863 J 113863 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The expression of the CXCR2 chemokine CXCL2 was upregulated in MH-S cells infected with modified vaccinia virus Ankara (MVA) but not MVA and vaccinia virus (VACV). MH-S cells constitutively generate the chemokines CCL3 and CCL5, as well as CCL2 and CCR1. Consequently, human monocyte THP and murine promyelocyte MPRO cells were stimulated to the same extent by supernatants from mock-treated and virus-infected MH-S cells. Chemotaxis of 1 cell. On the other hand, the CCR2-deficient human monocyte line U-937 substantially increased in chemotaxis when exposed to MVA-infected MH-S cell supernatants. The aforementioned cell types' chemotaxis is inhibited by J-113863 [1]. |
| ln Vivo | J-113863 (3-10 mg/kg; i.p.; once daily for 11 days; DBA-1 candle) dramatically lowers cellular respiration in joints and cures inflammation and joint degeneration associated with arthritic feet. |
| Animal Protocol |
Animal/Disease Models: Collagen Protein-induced DBA-1 male mice (10-12 weeks) [2] Doses: 3 mg/kg, 10 mg/kg Route of Administration: intraperitoneal (ip) injection; medium [2]. one time/day; for 11 days Experimental Results: Improved paw inflammation and joint damage, and Dramatically diminished joint cell infiltration. |
| References |
[1]. 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]. Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo. Br J Pharmacol. 2006 Nov;149(6):666-75. [3]. Design, synthesis, and discovery of a novel CCR1 antagonist. J Med Chem. 2001 Apr 26;44(9):1429-35. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~76.28 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5257 mL | 7.6285 mL | 15.2569 mL | |
| 5 mM | 0.3051 mL | 1.5257 mL | 3.0514 mL | |
| 10 mM | 0.1526 mL | 0.7628 mL | 1.5257 mL |