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].

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.