PF 04449613

Biological Activity

PF 04449613 is a potent PDE9 inhibitor (IC₅₀ = 22 nM). PF 4449613 shows more than 1000-fold selectivity for PDE9A over most of 79 other non-PDE targets investigated, except for cytochrome P450 2C19 (IC₅₀ = 1600 nM), dopamine transporter (K_i = 110 nM), μ-opioid receptor (K_i =3500 nM), and sodium channel binding site 2 (K_i =470 nM). PF 04449613 reduces body fat in mice with diet-induced obesity, stimulating mitochondrial activity in brown and white fat, and improving cardiometabolic syndrome symptoms. Brain penetrant. PF 04449613 increases synaptic calcium activity and learning-dependent synaptic plasticity in mice.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Additional Information

Background References

1. Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.
   Kleiman et al.
   J.Pharmacol.Exp.Ther., 2012;341:396
2. Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease.
   Lee et al.
   Nature, 2015;519:472
3. Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors.
   Claffey et al.
   J.Med.Chem., 2012;55:9055

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