PF-4136309 (INCB8761, PF-04136309) is a potent, selective, and orally bioavailable CCR2 antagonist with an IC50 of 5.2 nM for human CCR2.
PF-4136309 is potent in inhibiting CCR2 mediated signaling events such as intracellular calcium mobilization and ERK (extracellular signal-regulated kinase) phosphorylation. [1]
PF-4136309 exhibits >100-fold selectivity over other homologous chemokine receptors, a free fraction of 24% in human serum and 15% in mouse serum, and an oral bioavailability of 47% in mice, suitable as a tool compound for target validation in rodent models.[2]
[1] Xianming Deng, et, al. Eur J Med Chem. 2013;70:758-67. [2] Xue CB, et al. ACS Med Chem Lett. 2011 Oct 5;2(12):913-8.