CCR2 antagonist 5

CCR2 antagonist 5 is a selective, orally active hCCR2 inhibitor with good binding affinity (IC50=37 nM) and potent functional antagonism (chemotaxis IC50=30 nM). CCR2 antagonist 5 displays a Ki of 9.6 µM for mCCR2 binding. CCR2 antagonist 5 can be used in the research of inflammatory disease[1].

Signaling Pathways >> GPCR/G Protein >> CCR

Signaling Pathways >> Immunology/Inflammation >> CCR

Research Areas >> Inflammation/Immunology

hCCR2:37 nM (IC50)

mCCR2:9.6 μM (Ki)

CCR2 antagonist 5 (compound 8d) dose-dependently inhibits the influx of leukocytes, monocytes/macrophages and T-lymphocytes into the peritoneal cavity with an ED50 of 3 mg/kg p.o. bid in a thioglycollate-induced peritonitis (TG) model[1]. CCR2 antagonist 5 has good CV safety profile. It does not induce dose-dependent or notable effects on most cardiohemodynamic, functional respiratory and electrophysiological parameters up to 10 mg/kg (i.v.) with plasma level at 70 µM in an anesthetized dog[1]. CCR2 antagonist 5 has amendable oral bioavailability in dogs and primates. Pharmacokinetic parameters (p.o.)[1]: Species Dose (mg/kg) Cmax (ng/mL) AUClast (h*ng/mL) Oral bioavailability (%) dogs 6.7 1617 5887 70.2 non-human primates 7.2 740 3061 25.4 mice 10 74 204 19 rats 10 100 416 15.3

[1]. Zhang X, et al. Discovery of a 4-Azetidinyl-1-thiazoyl-cyclohexane CCR2 Antagonist as a Development Candidate. ACS Med Chem Lett. 2012 Oct 8;3(12):1039-44.