PF-2545920 |
| Catalog No.GC15194 |
A potent inhibitor of PDE10A
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1292799-56-4
Sample solution is provided at 25 µL, 10mM.
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PF-2545920 is an inhibitor of phosphodiesterase 10A (PDE10A) with IC50 value of 0.37nM [1].
PDE10A is highly expressed in the medium spiny neurons of the striatum and regulates both cGMP and cAMP. The PDE10A inhibitors are believed to regulate cyclic nucleotide signaling in the cortices-triatothalamic circuit. Previous inhibitors of PDE have potential therapeutic utility but also have potential safety risks due to off-target PDE inhibition. Thereby PF-2545920 is developed as a more selective inhibitor. PF-2545920 is shown to be efficacious both in vitro and in vivo with improved penetration in CNS. It has excellent in vivo efficacy in neurochemical elevation of cyclic nucleotides and in models predictive of antipsychotic activity. Administration of PF-2545920 to mice can cause increase in striatal cGMP with the minimal effective dose at about 1mg/kg [1].
References:
[1] Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, Marr ES, Menniti FS, Nelson F, O'Connor R, Pandit J, Proulx-Lafrance C, Schmidt AW, Schmidt CJ, Suiciak JA, Liras S. Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia. J Med Chem. 2009 Aug 27;52(16):5188-96.
| Cell experiment [1]: | |
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Cell lines |
Rat striatal cells |
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Preparation method |
The solubility of this compound in DMSO is >19.35 mg/ml. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
1 μM for 30 min at 30°C |
|
Applications |
Biochemical characterization of PF-2545920 showed that it could modulate both the dopamine D1-direct and D2-indirect striatal pathways and regulate the phosphorylation status of a panel of glutamate receptor subunits in the striatum. It was striking that PDE10A inhibition increased the phosphorylation of the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor GluR1 subunit at residue serine 845 at the cell surface. |
| Animal experiment [1]: | |
|
Animal models |
Male CF-1 mice or Sprague-Dawley rats |
|
Dosage form |
1-30 mg/kg, i.p. |
|
Application |
PF-2545920 was active in a range of antipsychotic models, antagonizing apomorphine-induced climbing in mice, inhibiting conditioned avoidance responding in both rats and mice, and blocking N-methyl-D-aspartate antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats, while improving baseline sensory gating in mice, all of which strengthen previously reported observations. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Grauer SM, et al. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther, 2009, 331(2), 574-590. | |
| Cas No. | 1292799-56-4 | SDF | |
| Chemical Name | 2-[[4-(1-methyl-4-pyridin-4-ylpyrazol-3-yl)phenoxy]methyl]quinoline | ||
| Canonical SMILES | CN1C=C(C(=N1)C2=CC=C(C=C2)OCC3=NC4=CC=CC=C4C=C3)C5=CC=NC=C5 | ||
| Formula | C25H20N4O | M.Wt | 392.45 |
| Solubility | ≥ 19.35 mg/mL in DMSO, ≥ 99.8 mg/mL in EtOH | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5481 mL | 12.7405 mL | 25.481 mL |
| 5 mM | 0.5096 mL | 2.5481 mL | 5.0962 mL |
| 10 mM | 0.2548 mL | 1.274 mL | 2.5481 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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