| 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[2].
As a cereblon-binding ligand-linker conjugate, Thalidomide-PEG3-COOH itself has no intrinsic biological activity; its function is to recruit the E3 ubiquitin ligase complex. When the terminal carboxylic acid is conjugated to a target protein ligand via an amide bond, the resulting PROTAC can simultaneously bind to both a target protein and cereblon, leading to ubiquitination and subsequent proteasomal degradation of the target. |
| 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 preclinical disease models.
|
| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. Its quality is confirmed by analytical methods such as HPLC and NMR, with a standard purity of ≥98%. The binding affinity of the final PROTAC construct to cereblon is typically determined by biophysical methods.
|
| Cell Assay |
N/A; this conjugate is not tested alone in cell-based assays. In a typical cellular assay for a complete PROTAC, cells are treated with the molecule, and target protein degradation is measured by Western blotting to determine the DC50 (half-maximal degradation concentration).
|
| Animal Protocol |
N/A; no animal studies are performed with the ligand-linker conjugate alone. For a complete PROTAC, in vivo studies are conducted using animal models. The compound is formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline for intraperitoneal (IP) or intravenous (IV) administration.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of 434.40, a molecular formula of C20H22N2O9, and is typically stored as a powder at -20degC for up to 3 years, protected from light. It is soluble in DMSO. The product requires protection from light during transportation and storage.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic or clinical applications. Standard chemical safety precautions should be observed during handling. The compound is a controlled substance in some jurisdictions.
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| References | |
| Additional Infomation |
The three-unit PEG linker provides a balance of hydrophilicity and flexibility, enhancing aqueous solubility and reducing steric hindrance in the formation of the ternary complex between the target protein, the PROTAC, and the E3 ligase. The terminal carboxylic acid allows for easy conjugation to target protein ligands containing primary amines via standard EDC/NHS chemistry.
|
| Molecular Formula |
C20H22N2O9
|
|---|---|
| Molecular Weight |
434.40
|
| Exact Mass |
434.132
|
| CAS # |
2682112-08-7
|
| PubChem CID |
162642708
|
| Appearance |
White to off-white solid powder
|
| Density |
1.437±0.06 g/cm3(Predicted)
|
| Boiling Point |
717.1±60.0 °C(Predicted)
|
| LogP |
-0.5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
31
|
| Complexity |
725
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C(CCC(N1)=O)N1C(C2C=CC(=CC=2C1=O)OCCOCCOCCC(=O)O)=O
|
| InChi Key |
PZDWKEFNXUZNPV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H22N2O9/c23-16-4-3-15(18(26)21-16)22-19(27)13-2-1-12(11-14(13)20(22)28)31-10-9-30-8-7-29-6-5-17(24)25/h1-2,11,15H,3-10H2,(H,24,25)(H,21,23,26)
|
| Chemical Name |
3-[2-[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]oxyethoxy]ethoxy]propanoic acid
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 :~250 mg/mL (~575.51 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3020 mL | 11.5101 mL | 23.0203 mL | |
| 5 mM | 0.4604 mL | 2.3020 mL | 4.6041 mL | |
| 10 mM | 0.2302 mL | 1.1510 mL | 2.3020 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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