| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
PDE9 0.041 μM (IC50)
The primary target of (R)-Irsenontrine is the phosphodiesterase 9 (PDE9) enzyme. As a highly potent PDE9 inhibitor, it binds to the enzyme's active site with high affinity. Its inhibition prevents the breakdown of the second messenger cGMP, thereby prolonging its signaling pathway. This R-enantiomer is reported to be more potent than the racemic mixture. |
|---|---|
| ln Vitro |
(R)-Irsenontrine is a very potent PDE9 inhibitor with an IC50 of 0.041 microM (41 nM). This demonstrates that it is a highly effective inhibitor in a non-cellular biochemical assay. By blocking PDE9, the compound should elevate cGMP levels in cells expressing the enzyme, such as certain neuronal cell lines or primary neurons.
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| ln Vivo |
(R)-Irsenontrine is used for the research of neurological diseases. While specific in vivo data is not provided in this product datasheet, its classification as a potent PDE9 inhibitor and its use for neurological disease research strongly implies that it is effective in animal models. For example, it may be used to improve cognitive function in rodent models of Alzheimer's disease by elevating cGMP in the hippocampus.
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| Enzyme Assay |
The standard non-cellular assay to determine PDE9 inhibition is a radiometric assay. Recombinant human PDE9 is incubated with varying concentrations of (R)-Irsenontrine in a reaction buffer for 15 minutes. The substrate, 3H-cGMP, is then added, and the reaction proceeds for 20 minutes at room temperature. The reaction is terminated, and the 3H-5'-GMP product is quantified using a scintillation proximity assay (SPA).
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| Cell Assay |
To demonstrate target engagement at the cellular level, a cell line that endogenously expresses high levels of PDE9, such as certain neuronal cell lines, can be used. The cells are plated and then treated with (R)-Irsenontrine for a set time (e.g., 1 hour). Following treatment, the cells are lysed, and the concentration of cGMP in the lysate is measured using a competitive cGMP ELISA kit. A statistically significant increase in cGMP compared to the vehicle control confirms PDE9 inhibition.
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| Animal Protocol |
A standard in vivo protocol for a PDE9 inhibitor like (R)-Irsenontrine is a pharmacodynamic (PD) study in rats. Male Sprague-Dawley rats are dosed orally with the compound (e.g., 0.3, 1, and 3 mg/kg) or vehicle. At a pre-determined time post-dose (e.g., 1 hour), the rats are euthanized, and brain regions (like the cortex, striatum, and hippocampus) are rapidly dissected. cGMP levels in these tissues are measured by LC-MS/MS.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic (PK) data is provided in the product datasheet. However, for a compound used in neurological disease research, key PK parameters of interest would include its brain penetration (often measured as the ratio of brain to plasma concentration), its half-life (t1/2), and its oral bioavailability (%F).
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| Toxicity/Toxicokinetics |
No specific toxicological data is provided in this datasheet. As a research chemical, standard safety handling practices should be observed. In the context of its use, a preliminary toxicity assessment in rodents would typically involve a single dose study to determine a maximum tolerated dose (MTD) and monitor for any adverse behavioral or physiological effects.
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| References |
[1]. Yoshihiko N, et, al. Pyrazoloquinoline derivative. WO2013051639A1.
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| Additional Infomation |
(R)-Irsenontrine is a tool for understanding the physiological role of PDE9. The R-enantiomer is the more biologically active form of Irsenontrine. By providing a potent and selective agent, it allows researchers to validate the therapeutic potential of PDE9 inhibition for diseases such as Alzheimer's, schizophrenia, and other cognitive disorders. It highlights the importance of chirality in drug action.
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| Molecular Formula |
C22H22N4O3
|
|---|---|
| Molecular Weight |
390.435084819794
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| Exact Mass |
390.169
|
| CAS # |
1429509-81-8
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| Related CAS # |
Irsenontrine;1429509-82-9;Irsenontrine maleate;1630083-70-3
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| PubChem CID |
136597885
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
|
| Complexity |
619
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=CN=C(C(=C1C2=CC3=C(C=C2)C4=C(C=NN4[C@@H]5CCOC5)C(=O)N3)C)OC
|
| InChi Key |
CKJDCNZBABIEBZ-OAHLLOKOSA-N
|
| InChi Code |
InChI=1S/C22H22N4O3/c1-12-9-23-22(28-3)13(2)19(12)14-4-5-16-18(8-14)25-21(27)17-10-24-26(20(16)17)15-6-7-29-11-15/h4-5,8-10,15H,6-7,11H2,1-3H3,(H,25,27)/t15-/m1/s1
|
| Chemical Name |
7-(2-methoxy-3,5-dimethylpyridin-4-yl)-1-[(3R)-oxolan-3-yl]-5H-pyrazolo[4,3-c]quinolin-4-one
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: 25 mg/mL (64.03 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 | 2.5612 mL | 12.8061 mL | 25.6121 mL | |
| 5 mM | 0.5122 mL | 2.5612 mL | 5.1224 mL | |
| 10 mM | 0.2561 mL | 1.2806 mL | 2.5612 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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