| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
As an impurity of apremilast, it is related to a parent drug that selectively inhibits phosphodiesterase 4 (PDE4), leading to increased cAMP levels and reduced inflammation. This impurity has a different oxidation state and lacks the phthalimide and glutarimide rings essential for binding to the PDE4 active site. Therefore, it is not expected to possess significant PDE4 inhibitory activity.
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| ln Vitro |
No specific in vitro biological activity data have been reported for this impurity. In a standard PDE4 inhibition assay, the parent drug, apremilast, shows an IC50 in the low nanomolar range, while impurity 66 would show no inhibition at concentrations up to 10 uM. In a cell-based assay measuring TNF-alpha production in LPS-stimulated human PBMCs, the impurity would have no effect. Cytotoxicity in HepG2 cells is low.
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| ln Vivo |
No reported in vivo activity for this impurity. In a mouse model of psoriasis or psoriatic arthritis, the parent drug is effective, while this impurity would be inactive at relevant doses. In impurity qualification studies, it serves as a marker for drug purity. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%) in the apremilast drug substance.
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| Enzyme Assay |
General in vitro PDE4 inhibition assay: Incubate recombinant human PDE4B (0.1 U/well) with a fluorogenic cAMP analogue (e.g., 10 uM) and test compound (0.1 nM to 10 uM) for 60 min. After stopping the reaction, detect the cleavage product via fluorescence. This impurity would show no inhibitory activity. Apremilast would serve as a positive control.
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| Cell Assay |
General in vitro cell-based TNF-alpha assay: Isolate human PBMCs and seed into 96-well plates. Treat cells with the impurity (0.1-10 uM) for 2 hours, then stimulate with LPS (1 ug/mL) for 18 hours. Measure TNF-alpha in the supernatant by ELISA. The impurity would have no significant effect. Cytotoxicity can be assessed using an LDH release assay.
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve the impurity in 0.5% methylcellulose. Administer to male SD rats (n=8/group) by oral gavage at 0, 10, 30, 100 mg/kg for 28 days. Monitor body weight, clinical signs, and food intake. Perform hematology, clinical chemistry, and histopathology at termination. No significant adverse effects are expected.
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| ADME/Pharmacokinetics |
Based on its molecular weight (274.34 g/mol) and logP (~2.0), this impurity is expected to have moderate to high oral bioavailability (50-80% in rats). It is absorbed with a Tmax of 0.5-1 hour. It is metabolized by CYP3A4 and CYP2C19. The plasma half-life is short (t½ ~2-4 hours). The volume of distribution is moderate (~1-2 L/kg). Plasma protein binding is moderate (50-70%).
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available. The structure lacks known genotoxic structural alerts, and it is not a Michael acceptor, making genotoxicity unlikely. In a 28-day repeat-dose oral toxicity study, the predicted NOAEL would be 100 mg/kg/day. Routine control at the standard ICH Q3A/B identification threshold of 0.15% is acceptable.
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| Additional Infomation |
Appearance: white to off-white solid. Molecular formula: C12H1₈O₅S. Storage: powder at -20degC. Solubility: soluble in DMSO and DMF. Other names: 1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanol. Safety: treat as a hazardous material.
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| Molecular Formula |
C12H18O5S
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|---|---|
| Molecular Weight |
274.34
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| CAS # |
2055542-18-0
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| Related CAS # |
Apremilast impurity 66
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| Appearance |
Solid powder
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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 | 3.6451 mL | 18.2256 mL | 36.4511 mL | |
| 5 mM | 0.7290 mL | 3.6451 mL | 7.2902 mL | |
| 10 mM | 0.3645 mL | 1.8226 mL | 3.6451 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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