PDE9 INHIBITOR PF-04447943

General description

A cell-permeable, blood-brain barrier permeant, pyrazolo[3,4 d]pyrimidinone compound that acts as a highly potent, selective, and active site-targeting inhibitor of phosphodiesterase 9A (PDE9A; K_i = 2.8 nM, 4.5 nM, and 18 nM for human, rhesus monkey, and rat recombinant PDE9A, respectively). Exhibits high selectivity over other phosphodiesterases (K_i = 8.6, 99, 50, 29, 14.9, 5.3, 75, 50, 51.2, and 80 µM for PDE1, PDE2A3, PDE3A, PDE4A, PDE5A, PDE6C, PDE7A2, PDE8A, PDE10, PDE11, respectively). Does not affect the activity of 60 other enzymes and receptors. Shown to diminish ANP-stimulated cGMP levels in human embryonic kidney cells expressing rhesus PDE9A2 (IC₅₀ = 375 nM). Shown to improve performance in novel object recognition in rats (~ 3 mg/kg, p.o.). Exhibits desirable pharmacokinetic properties with t_1/2 = 4.9 h, T_max = 0.3 h in rat.

A cell-permeable, blood-brain barrier permeant, pyrazolo[3,4 d]pyrimidinone compound that acts as a highly potent, selective, and active site-targeting inhibitor of phosphodiesterase 9A (PDE9A; K_i = 2.8 nM, 4.5 nM, and 18 nM for human, rhesus monkey, and rat recombinant PDE9A, respectively). Exhibits high selectivity over other phosphodiesterases (K_i = 8.6, 99, 50, 29, 14.9, 5.3, 75, 50, 51.2, and 80 µM for PDE1, PDE2A3, PDE3A, PDE4A, PDE5A, PDE6C, PDE7A2, PDE8A, PDE10, PDE11, respectively). Does not affect the activity of 60 other enzymes and receptors. Shown to diminish ANP-stimulated cGMP levels in human embryonic kidney cells expressing rhesus PDE9A2 (IC₅₀ = 375 nM). Shown to improve performance in novel object recognition in rats (~ 3 mg/kg, p.o.). Exhibits desirable pharmacokinetic properties with t_1/2 = 4.9 h, T_max = 0.3 h in rat.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
PDE9

Reversible: yes

Target IC₅₀: 2.8 nM, 4.5 nM and 18 nM for human, rhesus and rat PDE9A inhibition respectively

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Lee, D., et al. 2015. Nature.519, 472

Verhoest, P. R., et al. 2012. J. Med. Chem.55, 9045.

Hutson, P.H., et al. 2011. Neuropharmacology.61, 665.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany