INCB3284 bismesylate (INCB 3284, INCB003284) is a potent, selective and orally bioavailable hCCR2 antagonist with IC50 of 3.7 nM in antagonism of MCP-1 binding to hCCR2 and 4.7 nM in antagonism of chemotaxis activity.
INCB3284 potently inhibited CCR2-mediated signaling events such as intracellular calcium mobilization and ERK phosphorylation with IC50 values of 6 and 2.6 nM, respectively.
INCB3284 showed no significant inhibitory activity at a concentration of 1 μM against a panel of >50 ion channels, transporters, chemokine receptors including CCR1, CCR3, CCR5, CXCR3, and CXCR5, and additional GPCRs.
INCB3284 abolished the high salt (HS)-induced increase in BP in KL(+/-) mice, also attenuated the increased renal expressions of serum glucocorticoid-regulated kinase 1, thiazide-sensitive NaCl cotransporter, and ATP synthase β along with the renal structural damage and functional impairment induced by HS loading.