| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
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| Other Sizes |
| Targets |
Cereblon
CRBN (cereblon), an E3 ubiquitin ligase. |
|---|---|
| ln Vitro |
The two distinct ligands that make up PROTAC are linked together by a linker; one ligand binds to the E3 ubiquitin ligase, while the other binds to the target protein. Target proteins are specifically degraded by PROTAC through the intracellular ubiquitin-proteasome system [2].
As a cereblon-binding ligand-linker conjugate, Thalidomide-5-PEG3-NH2 hydrochloride itself has no intrinsic biological activity; its function is to recruit the E3 ubiquitin ligase complex. The terminal primary amine can be conjugated to a target protein ligand (or a linker attached to a target ligand) via amide bond formation using EDC/NHS or HATU coupling. 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 spacer that improves the aqueous solubility of the conjugate and the final PROTAC. The 5-position attachment site on the isoindole ring may preserve the binding affinity of the thalidomide core for cereblon better than modifications at the glutarimide nitrogen. |
| 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 ≥95-98%. 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 hydrochloride salt can be characterized by ion chromatography. The PEG3 spacer can be confirmed by NMR and mass spectrometry.
|
| 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 terminal primary amine is reacted with a carboxylic acid-containing target protein ligand using EDC and NHS activation. 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 hydrochloride salt form improves the water solubility of the conjugate, facilitating the conjugation 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.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of 441.86, a molecular formula of C19H24ClN3O7, and a standard purity of ≥95-98%. For storage, it should be kept as a powder at -20degC for up to 3 years, sealed, away from moisture and light. In a solvent, it can be stored at -80degC for 6 months or at -20degC for 1 month (sealed, away from moisture and light). It is soluble in DMSO. The IUPAC name is 2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)ethylamine hydrochloride. CAS: 2761385-81-1.
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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 product is stable under recommended storage conditions. It is not an approved therapeutic drug and has not been cleared for clinical use. Thalidomide is an immunomodulatory drug with known teratogenic effects; this derivative is for research purposes only and should be handled with appropriate caution.
|
| References | |
| Additional Infomation |
The 5-position attachment on the isoindole ring provides an alternative conjugation site that may preserve the binding affinity of the Thalidomide core for cereblon better than modifications at the glutarimide nitrogen. This design is based on the structure of PROTAC IRAK4 degrader-1, which utilizes a Thalidomide-5-linked PEG3-NH2 conjugate. The PEG3 linker provides a short, hydrophilic spacer that balances flexibility and solubility for many PROTAC applications. The hydrochloride salt form improves solubility and facilitates handling. This conjugate is a valuable building block for constructing cereblon-recruiting PROTACs with optimized linker lengths for specific target proteins.
|
| Molecular Formula |
C19H24CLN3O7
|
|---|---|
| Molecular Weight |
441.862764358521
|
| Exact Mass |
441.13
|
| CAS # |
2761385-81-1
|
| Related CAS # |
Thalidomide-5-PEG3-NH2;2743432-13-3
|
| PubChem CID |
166428255
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
30
|
| Complexity |
641
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C=C(C=C3)OCCOCCOCCN.Cl
|
| InChi Key |
GBYYYUKJOCCKAV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H23N3O7.ClH/c20-5-6-27-7-8-28-9-10-29-12-1-2-13-14(11-12)19(26)22(18(13)25)15-3-4-16(23)21-17(15)24;/h1-2,11,15H,3-10,20H2,(H,21,23,24);1H
|
| Chemical Name |
5-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione;hydrochloride
|
| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
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
|
|---|---|
| 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 | 2.2632 mL | 11.3158 mL | 22.6316 mL | |
| 5 mM | 0.4526 mL | 2.2632 mL | 4.5263 mL | |
| 10 mM | 0.2263 mL | 1.1316 mL | 2.2632 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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