| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; neo-substrates Ikaros (IKZF1) and Aiolos (IKZF3) for ubiquitination and degradation. |
|---|---|
| ln Vitro |
Thalidomide binds cereblon with moderate affinity (Kd ~10-20 uM). The PEG4 linker (4 ethylene glycol units) improves water solubility and provides a 1.5-2 nm spacer. The terminal amine (presented as hydrochloride salt) enables conjugation to carboxyl-containing target ligands. The compound alone induces degradation of Ikaros/Aiolos with lower potency than pomalidomide derivatives. In PROTACs, it recruits cereblon to degrade neo-targets.
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| ln Vivo |
Thalidomide-PEG4-NH2-derived PROTACs have shown in vivo efficacy in degrading various proteins (e.g., BRD4, CDK6) in mouse xenografts. The PEG4 linker offers good balance between solubility and permeability. The intermediate alone shows weak anti-myeloma activity due to cereblon binding, but it is primarily used as a building block. Specific in vivo data for this intermediate are limited.
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| Enzyme Assay |
Cereblon binding is assessed by TR-FRET. Recombinant CRBN-DDB1 protein is incubated with biotin-lenalidomide probe and thalidomide-PEG4-NH2 (0-500 uM). IC50 is typically 5-15 uM. The PEG4 chain slightly reduces binding (2-3 fold) compared to thalidomide alone due to steric hindrance. Binding is competitive and reversible.
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| Cell Assay |
Cells (e.g., MM.1S) are treated with thalidomide-PEG4-NH2 (1-100 uM) for 24-48 hours. Ikaros/Aiolos degradation is assessed by Western blot (DC50 ~10-30 uM). The compound alone has moderate antiproliferative activity (IC50 ~20-50 uM). For PROTAC testing, the conjugate is used at lower concentrations (1-1000 nM) to degrade target proteins.
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| Animal Protocol |
In vivo, PROTACs containing this building block are administered to xenograft mice (10-50 mg/kg, IV or IP). Tumor growth inhibition and target degradation are measured. The intermediate alone is sometimes tested as a control for non-specific effects. Thalidomide-PEG4-NH2 itself may cause mild tumor growth delay at high doses (100 mg/kg).
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| ADME/Pharmacokinetics |
Molecular weight: approximately 460 g/mol (free base) plus HCl. The PEG4 chain (MW ~176) provides water solubility >5 mg/mL. The hydrochloride salt enhances stability. The terminal amine has pKa ~9.5. The compound is stored at -20degC. Half-life in plasma is short (t1/2 ~1-2 hours) due to spontaneous hydrolysis of the thalidomide glutarimide ring.
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| Toxicity/Toxicokinetics |
Thalidomide and its derivatives are teratogenic and potentially neurotoxic. Acute toxicity in rodents: LD50 ~200-500 mg/kg for thalidomide. The PEG4-NH2 derivative likely has similar toxicity profile. Handle with extreme care: use gloves, avoid inhalation, and prevent contamination of work surfaces. The compound is for research only, not for human use.
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| References | |
| Additional Infomation |
This compound is a classic PROTAC building block. Thalidomide was originally marketed as a sedative but withdrawn due to teratogenicity; it was later found to bind cereblon and induce degradation of Ikaros/Aiolos, explaining its immunomodulatory activity. The PEG4-NH2 linker is widely used because of its optimal length. The hydrochloride salt improves handling. No clinical approval for this intermediate.
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| Molecular Formula |
C21H28CLN3O8
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|---|---|
| Molecular Weight |
485.915325164795
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| Exact Mass |
485.156
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| CAS # |
2387510-82-7
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| PubChem CID |
146018962
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
33
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| Complexity |
688
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)OCCOCCOCCOCCN.Cl
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| InChi Key |
NDHMOOQETYCWFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H27N3O8.ClH/c22-6-7-29-8-9-30-10-11-31-12-13-32-16-3-1-2-14-18(16)21(28)24(20(14)27)15-4-5-17(25)23-19(15)26;/h1-3,15H,4-13,22H2,(H,23,25,26);1H
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| Chemical Name |
4-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione;hydrochloride
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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 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)
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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 | 2.0580 mL | 10.2898 mL | 20.5795 mL | |
| 5 mM | 0.4116 mL | 2.0580 mL | 4.1159 mL | |
| 10 mM | 0.2058 mL | 1.0290 mL | 2.0580 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.
Products are for research use only; We do not sell to patients
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