| Description | CCX140 (CCX140-B) (CCX140-B) is an antagonist of CCR2. |
| In vitro | CCX140 inhibits the binding of 125I-CCL2 to monocytes with an IC50 value of 17 nM and it also inhibits CCL2-induced Ca2+ mobilization in monocytes with an IC50 value of 3 nM. CCX140 (CCX140-B) potently inhibits CCL2-induced chemotaxis of purified human blood monocytes with IC50 values of 8 nM in buffer and 200 nM in the presence of 100% human serum. CCX140 has a Kd value of 2.3 nM toward hCCR2. CCX140 also inhibits monocyte chemotaxis mediated by the other CCR2 ligands: CCL8/MCP-2, CCL7/MCP-3, and CCL13/MCP-4[1]. |
| In vivo | CCX140 also reduces urine output, glucose excretion, hepatic glycogen and triglyceride content and glucose 6-phosphatase levels[2]. Treatment of hCCR2 KI mice with CCX140 (CCX140-B) causes a dose-dependent reduction in the number of peritoneal leukocytes after thioglycollate challenge: CCX140 strongly blocks leukocyte infiltration at 30 mg/kg, partially blocks leukocyte infiltration at 10 mg/kg, and fails to block leukocyte infiltration at 3 mg/kg. In DIO mice, the CCR2 antagonist completely blocks the recruitment of inflammatory macrophages to visceral adipose tissue. In DIO hCCR2 KI mice, treatment with 100 mg/kg CCX140 blocks the progressive increase in UAER and ACR. CCX140 maintains lower UAER and ACR values during the entire 8-wk dosing regimen[1]. The mice exhibit reduced hyperglycemia and insulinemia, improved insulin sensitivity, increased circulating adiponectin levels, decreased pancreatic islet size and increased islet number. |
| Target activity | CCR5:7 μM (in Activated T lymphocytes), CCR2 (human):2.3 nM (kd)(in monocytes), CCR2:3 nM (in THP-1 cells) |
| Synonyms | 3-三氟甲基-4-氯-N-[2-[7H-吡咯并[2,3-D]嘧啶-4-羰基]-5-甲基-3-吡啶基]苯磺酰胺, CCX140-B |
| molecular weight | 495.86 |
| Molecular formula | C20H13ClF3N5O3S |
| CAS | 1100318-47-5 |
| Storage | keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: 0.25 mg/mL (0.50 mM), Sonication and heating are recommended. DMSO: 100 mg/mL (201.67 mM) |
| References | 1. Sullivan T, et al. CCR2 antagonist CCX140-B provides renal and glycemic benefits in diabetic transgenic human CCR2 knockin mice. Am J Physiol Renal Physiol. 2013 Nov 1;305(9):F1288-97. 2. Sullivan TJ, et al. Experimental evidence for the use of CCR2 antagonists in the treatment of type 2 diabetes. Metabolism. 2013 Nov;62(11):1623-32. |