1262238-11-8

INCB 3344 is an antagonist of chemokine (C-C motif) receptor 2 (CCR2; IC₅₀ = 10 nM in WEHI-274 murine monocytes). It is selective for CCR2 over a panel of G protein-coupled receptors, including CCR1 and CCR5, with IC₅₀s values greater than 1 μM. 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. 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.

[1]. brodmerkel c m, huber r, covington m, et al. discovery and pharmacological characterization of a novel rodent-active ccr2 antagonist, incb3344[j]. the journal of immunology, 2005, 175(8): 5370-5378.