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| Targets |
PDE2/PDE10-IN-1 targets phosphodiesterase 2 (PDE2) and phosphodiesterase 10 (PDE10), enzymes responsible for degrading cyclic nucleotides such as cAMP and cGMP. The compound has IC₅0 values of 29 nM for PDE2 and 480 nM for PDE10. It is a dual inhibitor of these two PDE isoforms, making it useful for studying cyclic nucleotide signaling in the brain.
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| ln Vitro |
PDE2/PDE10-IN-1 (compound 6) has IC50 values of 29 and 480 nM, respectively, which indicate that it inhibits PDE2 and PDE10. Additionally, PDE2/PDE10-IN-1 inhibits PDE4D and PDE11A, with IC50 values of 5890 nM and 6920 nM, respectively. Additionally, PDE2/PDE10-IN-1 did not significantly inhibit any of the CYP450 enzymes (CYP1A2, 2C9, 2D6, 2C19, and 3A4). PDE2/PDE10-IN-1 was likewise inactive in bacterial mutagenicity tests at concentrations as high as 125 μg/mL [1].
In vitro, PDE2/PDE10-IN-1 inhibits PDE2 with an IC₅0 of 29 nM and PDE10 with an IC₅0 of 480 nM. The compound demonstrates potent activity against PDE2 and moderate activity against PDE10. It is a dual inhibitor that modulates cyclic nucleotide levels by inhibiting both PDE2 and PDE10. Detailed cellular activity data are not extensively documented in the available literature. |
| ln Vivo |
Rats were given 2.5 mg/kg IV and 10 mg/kg po to study the PK characteristics of PDE2/PDE10-IN-1. Rapid clearance (t1/2=0.47 h) following intravenous administration was noted; this was surprising given the rat liver microsomes' (rLM) in vitro metabolic stability. It's interesting to note that PDE2/PDE10-IN-1 had good bioavailability and a maximum plasma concentration (Cmax) of 997 ng/mL following oral treatment, but with a longer clearance (t1/2=2.36 h). ). PDE2/PDE10-IN-1's ability to pass the blood-brain barrier was assessed in rats following a subcutaneous injection of 10 mg/kg. At pH > 3.5, PDE2/PDE10-IN-1 demonstrated satisfactory formulation with 10 to 20% HPβCD. Brain concentrations of PDE2/PDE10-IN-1, with high brain/plasma ratios and brain-free fractions, ranged from 370 to 895 ng/g one hour after treatment. More precisely, the 21 mg/kg PDE2 ED50 is occupied by the orally accessible PDE2/PDE10-IN-1 [1].
In vivo, PDE2/PDE10-IN-1 is orally bioavailable and occupies PDE2 with an ED₅0 of 21 mg/kg. The compound's oral bioavailability and ability to occupy PDE2 in vivo make it a valuable tool for neuroscience research. Further in vivo efficacy studies in animal models of neuropsychiatric and neurodegenerative disorders would be needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
The in vitro enzyme assay for PDE inhibition uses recombinant PDE2 and PDE10 enzymes. Enzyme activity is measured by incubating the enzyme with cyclic nucleotide substrate (cAMP or cGMP) and varying concentrations of the inhibitor. The amount of cyclic nucleotide hydrolyzed is quantified using scintillation proximity assays, fluorescence-based methods, or mass spectrometry. IC₅0 values are calculated from dose-response curves. Selectivity against other PDE isoforms may also be assessed.
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| Cell Assay |
For in vitro cell-based assays, cells expressing PDE2 and/or PDE10 (such as neuronal cell lines) are cultured and treated with PDE2/PDE10-IN-1 at various concentrations. Intracellular cyclic nucleotide levels (cAMP and cGMP) are measured by ELISA or immunoassay after compound treatment. Downstream signaling markers such as phosphorylated CREB or PKA substrates may be assessed by Western blot. Cells are maintained under standard culture conditions and experiments are typically performed in triplicate.
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| Animal Protocol |
In vivo animal studies for PDE2/PDE10-IN-1 typically involve rodent models of neuropsychiatric or neurodegenerative disorders. The compound is administered orally at various doses. Target engagement is assessed by measuring PDE2 occupancy using positron emission tomography (PET) with radiolabeled tracers or by ex vivo biochemical assays. Behavioral testing may be performed to assess cognitive function, motor activity, or anxiety-like behaviors. Brain tissue is collected for cyclic nucleotide measurements and biomarker analysis.
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| ADME/Pharmacokinetics |
PDE2/PDE10-IN-1 is orally bioavailable with an ED₅0 of 21 mg/kg for PDE2 occupancy. The compound has molecular weight 295.73 and molecular formula C1₅H10ClN₅. It is soluble in DMSO and typically formulated for oral administration in research settings. Further detailed PK parameters (half-life, Cmax, AUC) are not extensively documented in the available literature. The compound is stored as powder at -20degC.
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| Toxicity/Toxicokinetics |
Toxicological data for PDE2/PDE10-IN-1 are not well characterized in the public domain. As a research chemical, standard safety precautions should be observed. The compound is for laboratory use only and not intended for human therapeutic applications. PDE inhibitors as a class may have potential effects on cardiovascular and neurological function. Comprehensive toxicity profiling would be required for therapeutic development.
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| References | |
| Additional Infomation |
PDE2/PDE10-IN-1 (CAS# 1426833-08-0) is a dual phosphodiesterase inhibitor targeting PDE2 (IC₅0 = 29 nM) and PDE10 (IC₅0 = 480 nM). It is orally bioavailable and used in neuroscience research for studying schizophrenia, depression, and Huntington's disease. The compound is not approved for clinical use and is strictly for laboratory research purposes.
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| Molecular Formula |
C15H10CLN5
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| Molecular Weight |
295.726400852203
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| Exact Mass |
295.062
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| CAS # |
1426833-08-0
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| PubChem CID |
71295299
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| Appearance |
Off-white to brown solid powder
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| LogP |
3.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
21
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| Complexity |
381
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C12=NN=C(C3=CC=CC=C3Cl)N1C1C=NC=CC=1N=C2C
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| InChi Key |
SNQXTEAQGLZIDL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H10ClN5/c1-9-14-19-20-15(10-4-2-3-5-11(10)16)21(14)13-8-17-7-6-12(13)18-9/h2-8H,1H3
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| Chemical Name |
3-(2-chlorophenyl)-7-methyl-2,4,5,8,12-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene
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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 : ~12.5 mg/mL (~42.27 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3815 mL | 16.9073 mL | 33.8146 mL | |
| 5 mM | 0.6763 mL | 3.3815 mL | 6.7629 mL | |
| 10 mM | 0.3381 mL | 1.6907 mL | 3.3815 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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