| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
PF-05085727 targets phosphodiesterase 2A (PDE2A), a cyclic nucleotide phosphodiesterase that hydrolyzes both cGMP and cAMP. PDE2A is highly expressed in the brain, particularly in regions involved in cognition such as the cortex, hippocampus, and striatum. By inhibiting PDE2A, PF-05085727 prevents the breakdown of cGMP (and to a lesser extent cAMP), leading to elevated levels of these second messengers and enhanced downstream signaling pathways involved in synaptic plasticity, learning, and memory. PF-05085727 exhibits >4,000-fold selectivity for PDE2A over PDE1 and PDE3-11, ensuring minimal off-target effects on other phosphodiesterase isoforms.
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| ln Vitro |
PF-05085727 shown a low ability to induce cell death with an IC50 of 162 μM in cytotoxicity tests conducted on transformed human hepatic endothelial (THLE) cells [1]. The cytochrome P450 enzymes (CYP) that are least inhibited by PF-05085727 (3 μM) are 1A2, 2C8, 2C9, 2D6, and 3A4, which are inhibited by 16%, 18%, 7%, 4%, and 30%, respectively [1]. With IC50 values of 12.146 μM, 22,503 μM, 13.157 μM, and 6.515 μM, respectively, PF-05085727 (10 μM) suppresses PDE1B, PDE4B, PDE7B, and PDE10A[1].
PF-05085727 demonstrates potent in vitro activity against PDE2A with an IC50 of 2 nM. The compound shows weak activity with an IC50 of 162 μM to induce cell death in a cellular toxicity assay using transformed human liver endothelial (THLE) cells, indicating low cytotoxicity. PF-05085727 (3 μM) shows minimal inhibition of cytochrome P450 enzymes (CYPs), inhibiting 1A2, 2C8, 2C9, 2D6, and 3A4 with percentages of 16%, 18%, 7%, 4%, and 30%, respectively. 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, confirming its selectivity for PDE2A. |
| ln Vivo |
The unbound brain to unbound plasma (Cbu/Cpu) ratios of PF-05085727 (subcutaneous injection; 3.2 mg/kg/mouse; 3 mg/kg/rat) are around 0.27 and 0.37, respectively[1]. By using the enzyme-linked immunosorbent test, PF-05085727 in mice results in a significant and exposure-dependent rise in the accumulation of cGMP in the cortex, striatum, and hippocampus [1].
In vivo, PF-05085727 has been shown to increase cGMP accumulation in rodent brain regions. Following subcutaneous injection at 3.2 mg/kg in mice and 3 mg/kg in rats, the compound gives a ratio of unbound brain (Cbu) to unbound plasma (Cpu) of approximately 0.27 and 0.37, respectively, indicating good brain penetration. PF-05085727 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. The compound reverses the behavioral and electrophysiological effects of NMDA antagonists and demonstrates preclinical efficacy in cognitive models. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for PF-05085727 measures the inhibition of PDE2A enzymatic activity. Recombinant human PDE2A enzyme is incubated with varying concentrations of PF-05085727 (typically ranging from nanomolar to micromolar) in the presence of a fluorescent or radiolabeled cGMP substrate. The enzymatic reaction is monitored by measuring the hydrolysis of the substrate. The IC50 value of 2 nM is determined by fitting dose-response curves to the inhibition data. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against other PDE isoforms (PDE1, PDE3-11). Appropriate positive controls (known PDE inhibitors) and negative controls (DMSO vehicle) are included in each assay run.
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| Cell Assay |
The in vitro cellular assay for PF-05085727 is performed using cells expressing PDE2A, such as neuroblastoma cells or primary neurons. Cells are cultured in appropriate medium and treated with varying concentrations of PF-05085727 or vehicle control (DMSO). Cells are stimulated with agents that increase cGMP levels (e.g., nitric oxide donors or natriuretic peptides). Intracellular cGMP levels are measured using enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay. The potentiation of cGMP accumulation by PF-05085727 is quantified, and EC50 values are determined. The compound's effects on downstream signaling pathways (e.g., CREB phosphorylation) can also be assessed by Western blotting. Cytotoxicity is assessed using THLE cells (IC50 = 162 μM).
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| Animal Protocol |
In vivo animal experiments with PF-05085727 are conducted using rodents (mice and rats). The compound is administered via subcutaneous injection at doses of 3.2 mg/kg (mice) or 3 mg/kg (rats). Brain penetration is assessed by measuring compound concentrations in brain and plasma, and the Cbu/Cpu ratio is calculated (approximately 0.27 in mice and 0.37 in rats). cGMP levels in brain regions (cortex, striatum, hippocampus) are measured by ELISA. For cognitive studies, the compound is administered prior to behavioral testing (e.g., novel object recognition, Morris water maze) to assess effects on learning and memory. The compound's ability to reverse NMDA antagonist effects is also evaluated.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for PF-05085727 have been characterized. Following subcutaneous administration, the compound shows good brain penetration with Cbu/Cpu ratios of approximately 0.27 in mice and 0.37 in rats. PF-05085727 has a molecular weight of 413.40 and a chemical formula of C20H18F3N7. The compound is soluble in DMSO. The compound should be stored in a dry, dark environment at 0-4°C for short-term storage (days to weeks) or at -20°C for long-term storage (months to years). PF-05085727 shows minimal inhibition of CYP enzymes at 3 μM. Detailed PK parameters including half-life, clearance, and maximum concentration (Cmax) are available in the primary literature.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for PF-05085727 are partially documented. The compound shows weak activity with an IC50 of 162 μM to induce cell death in THLE cells, indicating low cytotoxicity. PF-05085727 shows minimal inhibition of cytochrome P450 enzymes at 3 μM. As a research-grade compound, PF-05085727 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not extensively documented and would require consultation of the primary literature or safety data sheets.
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| References | |
| Additional Infomation |
PF-05085727 is a research compound developed for studying the role of PDE2A in cognitive function and for evaluating PDE2A inhibition as a therapeutic strategy for cognitive disorders. The compound's high potency (IC50 = 2 nM), exceptional selectivity (>4,000-fold over other PDEs), and brain penetrant properties (Cbu/Cpu = 0.27-0.37) make it a valuable tool for dissecting PDE2A-specific functions in the brain. PF-05085727 has demonstrated preclinical efficacy in cognitive models, reversing NMDA antagonist effects and increasing cGMP accumulation in brain regions. The compound is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical neuroscience research. PF-05085727 is available from various chemical suppliers for research purposes.
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| Molecular Formula |
C20H18F3N7
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| Molecular Weight |
413.399033069611
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| Exact Mass |
413.157
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| CAS # |
1415637-72-7
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| PubChem CID |
71488864
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| Appearance |
White to yellow solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
608
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=NC(N2CCC2)=C2C(C3=C(C4=CC=C(C(F)(F)F)C=C4)N(C)N=C3)=NN(C)C2=N1
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| InChi Key |
SHAVEYUXRBIMLA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H18F3N7/c1-28-17(12-4-6-13(7-5-12)20(21,22)23)14(10-26-28)16-15-18(29(2)27-16)24-11-25-19(15)30-8-3-9-30/h4-7,10-11H,3,8-9H2,1-2H3
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| Chemical Name |
4-(Azetidin-1-yl)-1-methyl-3-(1-methyl-5-(4-(trifluoromethyl)-phenyl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidine
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| Synonyms |
PF-5085727; PF-05085727; PF 5085727; PF 05085727; PF5085727; PF05085727;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~151.19 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4190 mL | 12.0948 mL | 24.1896 mL | |
| 5 mM | 0.4838 mL | 2.4190 mL | 4.8379 mL | |
| 10 mM | 0.2419 mL | 1.2095 mL | 2.4190 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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