JNJ-41443532 (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). JNJ-41443532 displays a Ki of 9.6 µM for mCCR2 binding. JNJ-41443532 can be used in the research of inflammatory disease.
JNJ-41443532 (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].
JNJ-41443532 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].
JNJ-41443532 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 |