INCB 3344

INCB 3344 is an antagonist of chemokine (C-C motif) receptor 2 (CCR2; IC₅₀ = 10 nM in WEHI-274 murine monocytes).¹ It is selective for CCR2 over a panel of G protein-coupled receptors, including CCR1 and CCR5, with IC₅₀s values greater than 1 µM.² INCB 3344 inhibits chemotaxis of WEHI-274 cells induced by chemokine (C-C motif) ligand 2 (CCL2; IC₅₀ = 10 nM) and CCL2-induced phosphorylation of ERK in WEHI-274 cells.¹ It inhibits monocyte influx in a mouse model of peritonitis induced by thioglycolate when administered at doses of 60 and 100 mg/kg. INCB 3344 (30, 50, and 100 mg/kg twice per day) decreases the expression of CCR2 mRNA in the ear and reduces ear swelling in a mouse model of delayed-type hypersensitivity reaction. It prevents increases in or reduces macrophage levels in the spinal cord when administered at a dose of 100 mg/kg per day beginning the day of immunization or seven days following immunization, respectively, in a mouse model of experimental autoimmune encephalomyelitis (EAE). It also reduces disease incidence and severity in the same model and reduces disease severity in a rat model of adjuvant-induced arthritis. INCB 3344 reduces macrophage infiltration to the kidney and improves renal function in a mouse model of polycystic kidney disease.²

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1. Brodmerkel, C.M., Huber, R., Covington, M., et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J. Immunol. 175(8), 5370-5378 (2005).

2. Cassini, M.F., Kakade, V.R., Kurtz, E.S., et al. Mcp1 promotes macrophage-dependent cyst expansion in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 29(10), 2471-2481 (2018).