PF-05085727

PF-05085727 is a potent, selective and brain penetrant inhibitor of cGMP-dependent PDE2A (IC₅₀=2 nM). PF-05085727 inhibits PDE2A >4,000-fold selectivity over PDE1 and PDE3-11^[1]. IC50 & Target: IC50: 2 nM (PDE2A)^[1] In Vitro: PF-05085727 shows weak activity with IC₅₀ of 162 μM to induce cell death in a cellular toxicity assay using transformed human liver endothelial (THLE) cells^[1].
PF-05085727 (3 μM) shows a minimal inhibition of cytochrome P450 enzymes (CYPs), inhibits 1A2, 2C8, 2C9, 2D6 and 3A4 with percentage% of 16%, 18%, 7%, 4%, and 30%, respectively^[1].
PF-05085727 (10 μM) inhibits PDE1B, PDE4B, PDE7B and PDE10A with IC₅₀ values of 12.146 μM, 22,503 μM, 13.157 μM and 6.515 μM, respectively^[1].
In Vivo: PF-05085727 (subcutaneous injection; 3.2 mg/kg/mice; 3 mg/kg/rat) gives a ratio of unbound brain (C_bu) to unbound plasma (C_pu) of ca. 0.27 and 0.37, respectively^[1].
PF-05085727 in mice leads to an acute and exposure-dependent elevation in the accumulation of bulk levels of cGMP in cortex, striatum, and hippocampus as measured by enzyme-linked immunosorbent assay^[1].