| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Cereblon
CRBN (cereblon), an E3 ubiquitin ligase. |
|---|---|
| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
As a cereblon-binding ligand-linker conjugate, Pomalidomide-PEG3-azide itself has no intrinsic biological activity; its function is to recruit the E3 ubiquitin ligase complex. The azide group is a bioorthogonal handle that can react with alkyne-containing target protein ligands via CuAAc to form a stable triazole linkage. The resulting PROTAC can simultaneously bind to both a target protein and cereblon, leading to ubiquitination and subsequent proteasomal degradation of the target protein. The PEG3 linker provides a short, hydrophilic, and flexible connection, enhancing the water solubility of the conjugate and the final PROTAC. The azide click chemistry handle enables mild, selective conjugation under conditions that are compatible with a wide range of functional groups. |
| ln Vivo |
No specific in vivo activity has been reported for this conjugate alone; its in vivo degradation activity is observed only when conjugated to a target protein ligand to form a complete PROTAC molecule. The in vivo efficacy of such a PROTAC is typically evaluated in animal models of target-driven diseases.
|
| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. As a synthetic intermediate, its quality is confirmed by analytical methods such as HPLC and NMR, with a standard purity of ≥98%. Its binding affinity to cereblon is validated as part of a complete PROTAC construct using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The azide group can be characterized by its characteristic IR absorption at around 2100 cm-1. The IUPAC name is 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)acetamide.
|
| Cell Assay |
N/A; this conjugate is not tested alone in cell-based assays but is used as a building block for constructing PROTACs. In a typical conjugation step, the azide group is reacted with an alkyne-containing target protein ligand via CuAAc using CuSO4 and sodium ascorbate as catalyst in a THF/water mixture. The resulting PROTAC is then tested in target-expressing cancer cells for degradation activity by Western blotting to determine the DC50 (half-maximal degradation concentration). The PEG3 linker improves the water solubility of the reactants, facilitating the click chemistry reaction in aqueous buffers.
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| Animal Protocol |
N/A; no animal studies are performed with the ligand-linker conjugate alone. For in vivo studies of a complete PROTAC, the molecule is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered to animal models via intraperitoneal (IP) or intravenous (IV) injection. Target degradation in tissues and tumor growth inhibition are monitored. The PEG3 spacer may improve the pharmacokinetic properties of the conjugate by enhancing water solubility and reducing aggregation.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of 488.45, a molecular formula of C21H24N6O8, and a standard purity of ≥98%. The IUPAC name is 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)acetamide. For storage, it should be kept as a solid at -20degC for up to 3 years, sealed, away from moisture. It is soluble in DMSO. The product should be stored in a sealed container, protected from light. The azide group should be handled with care as it can be potentially explosive, especially in concentrated form or when exposed to heat or shock. CAS: 2267306-15-8.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or veterinary use. Standard chemical safety precautions should be followed during handling. The azide group should be handled with care to avoid premature reactions and potential explosion hazards. The product is stable under recommended storage conditions. It is not an approved therapeutic drug and has not been cleared for clinical use. Pomalidomide is an immunomodulatory drug (IMiD) clinically used for multiple myeloma; this derivative is for research purposes only. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license.
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| References | |
| Additional Infomation |
The PEG3 linker provides a short, hydrophilic spacer that balances solubility and flexibility, making it a widely used linker length in PROTAC design. The azide click chemistry handle enables CuAAc conjugation to alkyne-functionalized target ligands, providing a versatile and efficient conjugation strategy. This conjugate is a valuable building block for developing cereblon-recruiting PROTACs with optimized linker lengths for specific target proteins. The azide group also enables strain-promoted azide-alkyne cycloaddition (SPAAC) with DBCO-functionalized ligands for copper-free click chemistry.
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| Molecular Formula |
C21H24N6O8
|
|---|---|
| Molecular Weight |
488.450664520264
|
| Exact Mass |
488.165
|
| CAS # |
2267306-15-8
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| PubChem CID |
155292128
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| Appearance |
White to yellow solid powder
|
| LogP |
0.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
13
|
| Heavy Atom Count |
35
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| Complexity |
876
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)COCCOCCOCCN=[N+]=[N-]
|
| InChi Key |
DUTLUBRCOXPZLI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H24N6O8/c22-26-23-6-7-33-8-9-34-10-11-35-12-17(29)24-14-3-1-2-13-18(14)21(32)27(20(13)31)15-4-5-16(28)25-19(15)30/h1-3,15H,4-12H2,(H,24,29)(H,25,28,30)
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| Chemical Name |
2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]acetamide
|
| 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. |
| 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 :~200 mg/mL (~409.46 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0473 mL | 10.2365 mL | 20.4729 mL | |
| 5 mM | 0.4095 mL | 2.0473 mL | 4.0946 mL | |
| 10 mM | 0.2047 mL | 1.0236 mL | 2.0473 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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