| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Cereblon
The primary molecular target of Thalidomide-O-PEG4-amine hydrochloride is cereblon (CRBN), an E3 ubiquitin ligase substrate receptor. As a ligand for the E3 ubiquitin ligase complex, this compound binds to CRBN and recruits the ubiquitin-proteasome system. In the context of PROTAC technology, the thalidomide moiety serves as the E3 ligase recognition element, while the PEG4 linker connects to a second ligand that binds a target protein of interest. This bifunctional design enables the targeted degradation of specific proteins by bringing the target protein into proximity with the E3 ligase, leading to ubiquitination and subsequent proteasomal degradation. |
|---|---|
| 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].
In vitro studies demonstrate that Thalidomide-O-PEG4-amine hydrochloride functions as a key component in PROTAC molecules, where one ligand binds to the E3 ubiquitin ligase (cereblon/CRBN) and the other ligand binds to the target protein. The two ligands are joined by the PEG4 linker to form PROTACs that exploit the intracellular ubiquitin-proteasome system to specifically destroy target proteins. The PEG4 spacer enhances aqueous solubility and provides conformational flexibility, which is critical for the formation of the ternary complex between the target protein, PROTAC, and E3 ligase. This compound is designed for research applications in targeted protein degradation and chemical biology. |
| ln Vivo |
In vivo activity data for Thalidomide-O-PEG4-amine hydrochloride as a standalone compound are not extensively reported, as it is primarily utilized as a synthetic intermediate or linker component in PROTAC design rather than as a therapeutic agent itself. The in vivo efficacy of PROTAC molecules incorporating this linker would depend on the specific target protein ligand and the overall pharmacokinetic properties of the complete PROTAC construct. As a linker conjugate, its primary role is to facilitate targeted protein degradation in cellular and potentially in vivo settings through the ubiquitin-proteasome pathway.
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| Enzyme Assay |
The standard in vitro assay for evaluating this compound involves binding studies to assess its interaction with cereblon (CRBN), the E3 ubiquitin ligase substrate receptor. These assays typically employ surface plasmon resonance (SPR) or fluorescence polarization techniques to measure the binding affinity (Kd) between the thalidomide-based ligand and CRBN. Additionally, ternary complex formation assays can be performed to evaluate the ability of PROTAC molecules containing this linker to simultaneously engage both the E3 ligase and the target protein. Competition binding assays using fluorescently labeled probes are also commonly used to determine the inhibitory concentration (IC50) of the ligand for CRBN binding.
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| Cell Assay |
In vitro cell-based assays for Thalidomide-O-PEG4-amine hydrochloride typically involve its incorporation into PROTAC molecules followed by evaluation of target protein degradation in cultured cells. Cells are treated with PROTACs containing this linker, and the levels of the target protein are measured by Western blotting or immunofluorescence to assess degradation efficiency. Dose-response experiments are performed to determine the DC50 (half-maximal degradation concentration) of the PROTAC construct. Additionally, cell viability and proliferation assays may be conducted to evaluate the functional consequences of target protein degradation. The hydrochloride salt form improves solubility in cell culture media, facilitating compound handling and delivery.
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| Animal Protocol |
In vivo animal studies using Thalidomide-O-PEG4-amine hydrochloride are conducted as part of the evaluation of complete PROTAC molecules that incorporate this linker. Typical protocols involve administering PROTAC constructs to mouse xenograft models bearing tumors or disease-relevant tissues, followed by assessment of target protein degradation in harvested tissues via Western blot or immunohistochemistry. Pharmacodynamic endpoints include measurement of target protein levels, downstream signaling pathway modulation, and tumor growth inhibition in efficacy studies. Dosing regimens are optimized based on the pharmacokinetic properties of the specific PROTAC construct, with routes of administration typically including intravenous, intraperitoneal, or oral gavage.
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| ADME/Pharmacokinetics |
As a linker conjugate rather than a therapeutic drug, comprehensive pharmacokinetic data for Thalidomide-O-PEG4-amine hydrochloride alone are limited. However, the PEG4 moiety is known to enhance aqueous solubility and improve the pharmacokinetic profile of PROTAC molecules by increasing hydrophilicity and reducing aggregation. The hydrochloride salt form improves compound stability and handling characteristics. For PROTAC constructs incorporating this linker, pharmacokinetic parameters such as half-life, clearance, volume of distribution, and oral bioavailability would be determined by the complete molecule and are typically assessed in preclinical studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of Thalidomide-O-PEG4-amine hydrochloride as an individual compound is not extensively characterized, as it is primarily used as a research reagent and synthetic intermediate for PROTAC development. The compound is intended for research use only and is not approved for therapeutic use in humans. The thalidomide core structure is known to have teratogenic effects, and appropriate safety precautions should be taken when handling this compound. Standard laboratory safety practices, including the use of personal protective equipment and handling in a fume hood, are recommended.
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| References | |
| Additional Infomation |
Thalidomide-O-PEG4-amine hydrochloride (CAS 2820929-03-9) has a molecular formula of C23H32ClN3O9 and a molecular weight of 529.97. The compound appears as a colorless to yellow ointment and is soluble in DMSO at approximately 250 mg/mL (~471.72 mM). It should be stored at -20°C as a powder for up to 3 years or at 4°C for up to 2 years, protected from light and moisture. The compound is stable at ambient temperature for short periods during shipping. It is part of the PROTAC linker category and is used in E3 ligase ligand-linker conjugate applications.
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| Molecular Formula |
C23H32CLN3O9
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|---|---|
| Molecular Weight |
529.967885971069
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| Exact Mass |
529.182
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| CAS # |
2820929-03-9
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| Related CAS # |
Thalidomide-O-PEG4-amine;2401832-00-4;Thalidomide-O-PEG4-amine TFA;2934561-88-1
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| PubChem CID |
155292141
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| Appearance |
Colorless to yellow ointment
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
36
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| Complexity |
735
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C1C(CCC(N1)=O)N1C(C2C=CC=C(C=2C1=O)OCCOCCOCCOCCOCCN)=O
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| InChi Key |
IPABOZOPUWNLPC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H31N3O9.ClH/c24-6-7-31-8-9-32-10-11-33-12-13-34-14-15-35-18-3-1-2-16-20(18)23(30)26(22(16)29)17-4-5-19(27)25-21(17)28;/h1-3,17H,4-15,24H2,(H,25,27,28);1H
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| Chemical Name |
4-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). 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 :~250 mg/mL (~471.72 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 | 1.8869 mL | 9.4345 mL | 18.8690 mL | |
| 5 mM | 0.3774 mL | 1.8869 mL | 3.7738 mL | |
| 10 mM | 0.1887 mL | 0.9434 mL | 1.8869 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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