| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; neo-substrates Ikaros (IKZF1) and Aiolos (IKZF3). |
|---|---|
| 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. PROTACs target and selectively degrade target proteins by taking advantage of the intracellular ubiquitin-proteasome system.
Thalidomide binds cereblon with moderate affinity (Kd ~10-20 uM). The 4-O-C2-NH2 modification introduces a short, hydrophilic spacer (2 carbons + oxygen). The terminal amine (as hydrochloride) enables conjugation to carboxyl-containing target ligands. The compound alone induces mild degradation of Ikaros/Aiolos. The short C2 spacer positions the amine close to the thalidomide core, which may affect conjugation efficiency and ternary complex formation in PROTACs. |
| Enzyme Assay |
Cereblon binding is measured by TR-FRET. Thalidomide-4-O-C2-NH2 (0-500 uM) is incubated with CRBN-DDB1 and a fluorescent probe. IC50 is typically 10-30 uM. The C2-NH2 group may slightly reduce binding affinity (2-3 fold) compared to thalidomide due to steric hindrance at the 4-position, but it remains useful for PROTAC synthesis.
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| Cell Assay |
Cells (e.g., MM.1S) are treated with the compound alone (1-100 uM) for 24-48 hours. Ikaros/Aiolos degradation is assessed by Western blot (DC50 ~20-50 uM). The compound shows moderate antiproliferative activity (IC50 ~30-60 uM). For PROTACs, the conjugate is tested at lower concentrations (1-1000 nM) for degradation of the target of interest.
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| Animal Protocol |
In vivo, PROTACs derived from this building block are administered to xenograft mice (10-50 mg/kg, IV). The intermediate alone is sometimes dosed as a control. The short C2 linker may result in rapid clearance of the final PROTAC due to hydrophilicity. PK parameters depend on the specific warhead. Tumor tissue is analyzed for target degradation.
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| ADME/Pharmacokinetics |
Molecular weight: approximately 350 g/mol (free base) plus HCl. The C2-NH2 chain (MW ~44) increases water solubility. The hydrochloride salt is stable. The compound is stored at -20degC. The thalidomide glutarimide ring hydrolyzes in aqueous buffer (t1/2 ~1-2 hours at pH 7.4, 37degC). The 4-O-C2-NH2 group does not prevent hydrolysis.
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| Toxicity/Toxicokinetics |
Thalidomide derivatives are teratogenic and potentially neurotoxic. The C2-NH2 modification does not reduce this risk. Acute toxicity in rodents: LD50 ~200-500 mg/kg for thalidomide. Handle with extreme caution: use double gloves, fume hood, and dedicated work area. Not for human use. The compound is for research only.
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| References | |
| Additional Infomation |
This PROTAC building block features a thalidomide core with a 4-O-C2-NH2 linker. The 4-position is one of the preferred sites for derivatization because it does not completely disrupt cereblon binding. The C2 spacer is the shortest possible (ethylamine). This compact linker may be useful for targets where a longer spacer would prevent ternary complex formation. Compare to PEG-containing linkers which offer greater solubility. No clinical approval.
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| Molecular Formula |
C15H16CLN3O5
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|---|---|
| Molecular Weight |
353.757642745972
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| Exact Mass |
353.077
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| CAS # |
2341840-99-9
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| PubChem CID |
138991788
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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 |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
549
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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)OCCN.Cl
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| InChi Key |
AZQNUQDFOMUSBB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H15N3O5.ClH/c16-6-7-23-10-3-1-2-8-12(10)15(22)18(14(8)21)9-4-5-11(19)17-13(9)20;/h1-3,9H,4-7,16H2,(H,17,19,20);1H
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| Chemical Name |
4-(2-aminoethoxy)-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, 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 :~125 mg/mL (~353.35 mM)
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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 | 2.8268 mL | 14.1339 mL | 28.2678 mL | |
| 5 mM | 0.5654 mL | 2.8268 mL | 5.6536 mL | |
| 10 mM | 0.2827 mL | 1.4134 mL | 2.8268 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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