| Description | RS102895 is a potent CCR2 antagonist (IC50: 360 nM) and shows no effect on CCR1. |
| In vitro | RS102895同时抑制人体α1a、α1d受体和大鼠脑皮质5HT1a受体，其半抑制浓度(IC50)分别为130、320、470 nM。此外，RS102895对野生型及D284N突变的MCP-1受体有抑制作用，IC50分别为550 nM和568 nM，对D284A突变的MCP-1受体抑制作用较弱（IC50为1892 nM），而对E291A, E291Q, D284A/E291A或D284N/E291Q无影响（IC50均超过100,000 nM）[1]。RS102895通过抑制CCR2，在10 μM浓度下改善了细胞外基质蛋白的表达增加，并在高糖刺激的系膜细胞（MCs）中，1 μM或10 μM的浓度显著阻断了纤维连接蛋白和IV型胶原蛋白的表达。10 μM的RS102895还能消除MCP-1处理后MCs中TGF-β1水平的增加[2]。 |
| In vivo | RS102895 (3 g/L) 通过脊髓内注射在术后第3至9天导致患有骨癌痛(BCP)的大鼠痛阈逐渐降低，但在12天后痛阈有所增加。RS102895还能有效逆转脊髓中NR2B、nNOS与SIGIRR表达的模式[3]。 |
| Target activity | 5-HT1A:470 nM, CCR2:360 nM, α1D-adrenoceptor (human):320 nM, α1A-adrenoceptor:130 nM |
| molecular weight | 390.4 |
| Molecular formula | C21H21F3N2O2 |
| CAS | 300815-41-2 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 15 mg/mL (38.42 mM) |
| References | 1. Mirzadegan T, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle. J Biol Chem. 2000 Aug 18;275(33):25562-71. 2. Park J, et al. MCP-1/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells. Am J Physiol Renal Physiol. 2008 Sep;295(3):F749-57. 3. Ren F, et al. Analgesic Effect of Intrathecal Administration of Chemokine Receptor CCR2 Antagonist is Related to Change in Spinal NR2B, nNOS, and SIGIRR Expression in Rat with Bone Cancer Pain. Cell Biochem Biophys. 2015 Jun;72(2):611-6. |