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Biological Activity for PF 04449613
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 (Ki = 110 nM), μ-opioid receptor (Ki =3500 nM), and sodium channel binding site 2 (Ki =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.
Sold for research purposes under agreement from Pfizer Inc.
Compound Libraries for PF 04449613
Technical Data for PF 04449613
|Storage||Store at -20°C|
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.
Solubility Data for PF 04449613
|Solvent||Max Conc. mg/mL||Max Conc. mM|
|1eq. HCl||3.95||10 with gentle warming|
Preparing Stock Solutions for PF 04449613
The following data is based on the product molecular weight 395.45. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||2.53 mL||12.64 mL||25.29 mL|
|5 mM||0.51 mL||2.53 mL||5.06 mL|
|10 mM||0.25 mL||1.26 mL||2.53 mL|
|50 mM||0.05 mL||0.25 mL||0.51 mL|
References for PF 04449613
References are publications that support the biological activity of the product.
Kleiman et al (2012) Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo. J.Pharmacol.Exp.Ther. 341 396 PMID: 22328573
Lee et al (2015) Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease. Nature 519 472 PMID: 25799991
Claffey et al (2012) Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors. J.Med.Chem. 55 9055 PMID: 23025719
Mishra et al (2021) Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice. J.Clin.Invest. 131 e148798 PMID: 34618683
Lai et al (2018) The phosphodiesterase 9 inhibitor PF-04449613 promotes dendritic spine formation and performance improvement after motor learning. Dev.Neurobiol. 78 859 PMID: 30022611
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Citations for PF 04449613
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