INCB 3284 dimesylate is a selective and orally bioavailable human CCR2 antagonist, inhibiting monocyte chemoattractant protein-1 binding to hCCR2 (IC50: 3.7 nM). It can be used in the research of acute liver failure.

MCP-1-hCCR2:3.7 nM

INCB 3284 causes an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 μM in inhibition of the hERG potassium current. However, INCB 3284 has no effec on CCR1, CCR3, CCR5, CXCR3, and CXCR5, or additional GPCRs at a concentration of 1 μM. Moreover, INCB 3284 potently inhibits CCR2-mediated signaling events such as intracellular calcium mobilization and ERK phosphorylation with IC50 values of 6 and 2.6 nM, respectively.INCB 3284 dimesylate is a pentent, selective and orally bioavailable human CCR2 antagonist, inhibiting monocyte chemoattractant protein-1 binding to hCCR2, with an IC50 of 3.7 nM.?INCB 3284 also causes an IC50 of 4.7 nM in antagonism of chemotaxis activity, an IC50 of 84 μM in inhibition of the hERG potassium current.?However, INCB 3284 has no effec on CCR1, CCR3, CCR5, CXCR3, and CXCR5, or additional GPCRs at a concentration of 1 μM.?Moreover, INCB 3284 potently inhibits CCR2-mediated signaling events such as intracellular calcium mobilization and ERK phosphorylation with IC50 values of 6 and 2.6 nM, respectively.

INCB 3284 effectively diminishes the ratio of phosphorylated ERK1/2 (pERK1/2) to total ERK1/2 (tERK1/2), alongside reducing G-protein signaling pathway activity and the production of proinflammatory cytokines in cortex lysates of mice treated with azoxymethane. Additionally, administered at a dosage of 1 mg/kg/day intraperitoneally, it alleviates liver damage and curtails microglia activation in azoxymethane (AOM)-treated mice through the inhibition of CCR2.