| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
TAK-915 targets phosphodiesterase 2A (PDE2A), an enzyme that hydrolyzes cyclic AMP (cAMP) and cyclic GMP (cGMP). PDE2A is highly expressed in the brain and is involved in the regulation of cognitive function, learning, and memory. By inhibiting PDE2A, TAK-915 increases cAMP and cGMP levels in the brain, enhancing synaptic plasticity and cognitive function.
|
|---|---|
| ln Vitro |
TAK-915 is a potent PDE2A inhibitor with an IC50 of 0.61 nM. It shows >4100-fold selectivity for PDE2A over PDE1A. The compound is brain-penetrant and orally active. Its high potency and selectivity make it a valuable tool for studying the role of PDE2A in cognitive function and for developing treatments for cognitive disorders.
|
| ln Vivo |
In the Morris water maze task, TAK-915 (3 mg/kg; oral; daily; for 4 days; male F344 rats) therapy dramatically reduced the escape latency of elderly rats [2]. Oral TAK-915 (1, 3 and 10 mg/kg) reduces memory deficits in rats caused by the non-selective muscarinic antagonist scopolamine in a dose-dependent manner [2]. When TAK-915 (Compound 36) was given orally to mice at doses of 3 or 10 mg/kg, the levels of cyclic guanosine monophosphate (cGMP) increased in a dose-dependent manner [1].
TAK-915 is orally active and brain-penetrant. In vivo studies have demonstrated its potential for the treatment of cognitive and neuropsychiatric disorders, including memory and learning impairments. Specific animal model data and dosing regimens are not extensively detailed in the provided search results. |
| Enzyme Assay |
TAK-915's inhibition of PDE2A can be assessed using in vitro enzyme assays. Recombinant PDE2A enzyme is incubated with its substrate (cAMP or cGMP) in the presence of varying concentrations of TAK-915. The amount of hydrolyzed product (AMP or GMP) is measured using a suitable detection method (e.g., ELISA, radiometric, or mass spectrometry) to determine the IC50. Selectivity over other PDE isoforms (e.g., PDE1A, PDE3A, PDE4D) is assessed using similar assays.
|
| Cell Assay |
The cellular activity of TAK-915 is evaluated in cells expressing PDE2A, such as neuronal cell lines or primary neurons. Cells are treated with increasing concentrations of TAK-915, and the levels of cAMP and cGMP are measured by ELISA or LC-MS/MS. The effect of PDE2A inhibition on downstream signaling pathways (e.g., CREB phosphorylation, synaptic protein expression) can also be assessed.
|
| Animal Protocol |
Animal/Disease Models: Male F344 rats (10 weeks and 26 months old) performed Morris water maze task [2]
Doses: 3 mg/kg Route of Administration: po (po (oral gavage)) Daily; lasted 4 days. Experimental Results: The escape latency of aged rats was Dramatically shortened in the Morris water maze task. TAK-915 is administered orally to animal models of cognitive disorders. In rodent models of cognitive impairment (e.g., scopolamine-induced amnesia, aged rats, or transgenic models of Alzheimer's disease), TAK-915 is given at various doses via oral gavage. Cognitive function is assessed using behavioral tests such as the Morris water maze, novel object recognition, or passive avoidance tests. Brain levels of cAMP and cGMP are measured to confirm target engagement. |
| ADME/Pharmacokinetics |
TAK-915 has a molecular weight of 458.36 and molecular formula C19H18F4N4O5. It is a potent, selective, brain-penetrant, and orally active PDE2A inhibitor. Specific physicochemical properties such as solubility and logP are not extensively detailed in standard reference sources.
|
| Toxicity/Toxicokinetics |
The toxicity profile of TAK-915 is not extensively documented. As a PDE2A inhibitor, potential adverse effects may include cardiovascular effects (as PDEs are involved in cardiac function) and CNS effects. Specific LD50 values and organ-specific toxicity data are not readily available.
|
| References |
|
| Additional Infomation |
TAK-915 (CAS# 1476727-50-0) is a potent, selective, brain-penetrant, and orally active phosphodiesterase 2A (PDE2A) inhibitor with an IC50 of 0.61 nM. It shows >4100-fold selectivity for PDE2A over PDE1A. The compound has been developed for the treatment of cognitive disorders and is a research tool for studying PDE2A function in the brain.
|
| Molecular Formula |
C19H18F4N4O5
|
|---|---|
| Molecular Weight |
458.363638401031
|
| Exact Mass |
458.121
|
| CAS # |
1476727-50-0
|
| PubChem CID |
72190879
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
651.0±55.0 °C at 760 mmHg
|
| Flash Point |
347.5±31.5 °C
|
| Vapour Pressure |
0.0±1.9 mmHg at 25°C
|
| Index of Refraction |
1.539
|
| LogP |
1.78
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
670
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
COC[C@H](C1=CC(=C(C=C1)OC(F)(F)F)F)NC(=O)N2CC(=O)NC3=C2N=CC(=C3)OC
|
| InChi Key |
AWJSRXUQLSPAOI-CQSZACIVSA-N
|
| InChi Code |
InChI=1S/C19H18F4N4O5/c1-30-9-14(10-3-4-15(12(20)5-10)32-19(21,22)23)26-18(29)27-8-16(28)25-13-6-11(31-2)7-24-17(13)27/h3-7,14H,8-9H2,1-2H3,(H,25,28)(H,26,29)/t14-/m1/s1
|
| Chemical Name |
N-[(1S)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl]-7-methoxy-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~7.5 mg/mL (~16.36 mM)
|
|---|---|
| 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 | 2.1817 mL | 10.9085 mL | 21.8169 mL | |
| 5 mM | 0.4363 mL | 2.1817 mL | 4.3634 mL | |
| 10 mM | 0.2182 mL | 1.0908 mL | 2.1817 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
