INCB 3344

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.Formal Name: rel-N-[2-[[(3R,4R)-1-[trans-4-(1,3-benzodioxol-5-yl)-4-hydroxycyclohexyl]-4-ethoxy-3-pyrrolidinyl]amino]-2-oxoethyl]-3-(trifluoromethyl)-benzamide. CAS Number: 1262238-11-8. Molecular Formula: C29H34F3N3O6. Formula Weight: 577.6. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMSO: soluble. SMILES: CCO[C@@H]1[C@@H](NC(CNC(C2=CC=CC(C(F)(F)F)=C2)=O)=O)CN([C@]3([H])CC[C@@](C4=CC=C(OCO5)C5=C4)(O)CC3)C1. InChi Code: InChI=1S/C29H34F3N3O6/c1-2-39-25-16-35(21-8-10-28(38,11-9-21)19-6-7-23-24(13-19)41-17-40-23)15-22(25)34-26(36)14-33-27(37)18-4-3-5-20(12-18)29(30,31)32/h3-7,12-13,21-22,25,38H,2,8-11,14-17H2,1H3,(H,33,37)(H,34,36)/t21-,22-,25-,28-/m0/s1. InChi Key: MZEOSVPWMSEFPW-UTWBDPIXSA-N.