| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
PKR (Protein Kinase R) and PERK (Protein Kinase R-like Endoplasmic Reticulum Kinase). WAY-354896 activates both of these serine/threonine kinases. PKR is activated by double-stranded RNA (viral infection), while PERK is activated by unfolded proteins in the ER. Their activation leads to the phosphorylation of eIF2alpha (eukaryotic initiation factor 2 alpha), reducing general protein translation while allowing the translation of specific stress-response genes.
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| ln Vitro |
WAY-354896 is a dual activator of PKR and PERK. By activating these kinases, it directly induces the phosphorylation of eIF2alpha (eukaryotic initiation factor 2 alpha). This leads to a reduction in cap-dependent translation and an increase in the expression of stress-related transcription factors like ATF4. As a pharmacological tool, it can induce the unfolded protein response (UPR) and integrated stress response (ISR) in cells.
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| ln Vivo |
No specific in vivo data has been reported. As a dual activator, it would be used in animal models to study the physiological effects of activating the integrated stress response. This could be in models of cancer (to induce apoptosis), neurological disease (ER stress plays a role), or metabolic disorders. The compound is a chemical tool, not a drug candidate.
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| Enzyme Assay |
WAY-354896 is a dual activator of PKR and PERK. A typical kinase activation assay is performed using purified PKR or PERK enzymes and an eIF2alpha substrate. The enzyme is incubated with various concentrations of WAY-354896 (0.1-100 uM) in a reaction buffer (20 mM HEPES, pH 7.4, 50 mM KCl, 5 mM MgCl2, 2 mM DTT, 100 uM ATP) for 30 minutes at 30degC. The reaction is stopped, and the phosphorylation level of the eIF2alpha substrate is measured using a specific anti-phospho-eIF2alpha (Ser51) antibody in a Western blot or via an ELISA-based detection kit. A dose-dependent increase in signal indicates activation. The EC50 for activation can be determined.
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| Cell Assay |
For in vitro cellular studies, HeLa or HEK293T cells are seeded in 6-well plates (5×10⁵ cells/well). Cells are treated with WAY-354896 (1-50 uM) for 4-24 hours. Cells are then lysed, and protein lysates are prepared. The activation of the stress response is measured by Western blotting for phosphorylated eIF2alpha (p-eIF2alpha) and by measuring the expression of downstream effectors like ATF4 (activating transcription factor 4) and CHOP (C/EBP homologous protein, a pro-apoptotic factor). DMSO-treated cells serve as a negative control. Thapsigargin or tunicamycin (ER stress inducers) can serve as positive controls for PERK activation. Cell viability is assessed by MTT assay after 48 hours of treatment.
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| Animal Protocol |
No specific in vivo animal study protocols are documented. For a compound that induces ER stress, a typical protocol would involve intraperitoneal (i.p.) injection of WAY-354896 (e.g., 10-50 mg/kg) into 6-8 week old male C57BL/6 mice. Tissues (liver, pancreas, brain) would be harvested 4-12 hours post-dose. The activation of the ISR would be assessed by Western blotting for p-eIF2alpha in tissue lysates. To study functional outcomes, such as insulin secretion, the compound could be injected into a mouse model of diabetes, and blood glucose levels monitored.
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| ADME/Pharmacokinetics |
No pharmacokinetic data has been reported. WAY-354896 is a flavonolignan derivative with a molecular weight of 312.31 g/mol. This suggests it may have favorable drug-like properties, including the ability to cross membranes. However, its specific ADME (absorption, distribution, metabolism, excretion) properties are unknown and would require experimental determination. Its solubility in DMSO is >10 mM, which is adequate for in vivo formulation.
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| Toxicity/Toxicokinetics |
No specific toxicity data has been reported. However, as an activator of the PERK/PKR/eIF2alpha pathway, chronic activation can lead to cell death (apoptosis). Therefore, high doses or long-term exposure could be cytotoxic to normal cells, particularly in tissues sensitive to ER stress, such as the pancreas (beta cells) and liver. This is a potential mechanism-based toxicity. The compound is for research use only.
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| Additional Infomation |
WAY-354896 is a dual activator that can be used to induce the integrated stress response (ISR) in cells. It belongs to the chemical class of flavonolignans. The molecular formula is C18H16O5, with a molecular weight of 312.31. It is also known as 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-4H-pyran-4-one derivative. It is a valuable chemical probe for studying cellular stress signaling pathways like the unfolded protein response (UPR).
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| Molecular Formula |
C18H16O5
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|---|---|
| Molecular Weight |
312.32
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| Exact Mass |
312.099
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| Elemental Analysis |
C, 69.22; H, 5.16; O, 25.61
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| CAS # |
136498-37-8
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| PubChem CID |
2917176
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
489.3±45.0 °C at 760 mmHg
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| Flash Point |
218.2±28.8 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.597
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| LogP |
3.51
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
23
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| Complexity |
439
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C2=CC=C3OCCOC3=C2)OC2=CC=C(OC)C=C2C(=O)C1
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| InChi Key |
VPUHJQWPTZSKEP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H16O5/c1-20-12-3-5-15-13(9-12)14(19)10-17(23-15)11-2-4-16-18(8-11)22-7-6-21-16/h2-5,8-9,17H,6-7,10H2,1H3
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| Chemical Name |
2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-methoxychroman-4-one
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| Synonyms |
WAY-354896; WAY 354896; WAY354896
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.2018 mL | 16.0092 mL | 32.0184 mL | |
| 5 mM | 0.6404 mL | 3.2018 mL | 6.4037 mL | |
| 10 mM | 0.3202 mL | 1.6009 mL | 3.2018 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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