| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The compound targets cereblon (CRBN), an E3 ubiquitin ligase substrate receptor within the CUL4-RBX1-DDB1-CRBN complex. The thalidomide-based ligand binds to CRBN, recruiting the E3 ubiquitin ligase machinery. When the compound is conjugated to a target protein ligand, the resulting bifunctional PROTAC molecule brings the target protein into proximity with the E3 ligase, leading to target ubiquitination and subsequent degradation by the 26S proteasome. The PEG6 linker provides sufficient length and flexibility to accommodate various distances between CRBN and different target proteins.
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| ln Vitro |
In vitro activity is realized through the use of this compound as a PROTAC building block. When conjugated to a target protein-binding ligand, the resulting PROTAC induces selective target protein ubiquitination and proteasome-dependent degradation. The ligand-linker conjugate alone shows minimal intrinsic biological activity. In cellular assays, PROTACs constructed with this linker (such as THAL-SNS-032) demonstrate potent target protein degradation at nanomolar concentrations. Standard validation involves treating cells with the PROTAC at varying concentrations (0.001-10 uM) for 4-24 hours, followed by Western blot analysis to quantify target protein levels. DC50 values (concentration for 50% degradation) are typically in the low nanomolar to sub-micromolar range depending on the target.
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| ln Vivo |
In vivo efficacy studies with PROTACs incorporating the PEG6 linker are typically performed using murine xenograft models. Complete PROTAC molecules are administered to tumor-bearing immunodeficient mice via intraperitoneal (IP) or intravenous (IV) routes at doses ranging from 1-30 mg/kg, often on a daily or every-other-day regimen for 2-4 weeks. The PEG6 linker provides moderate hydrophilicity that facilitates aqueous formulation while maintaining sufficient cell permeability. Efficacy is assessed by tumor volume measurements (using calipers every 2-3 days), body weight monitoring, and Western blot/IHC analysis of target protein degradation in harvested tumor tissue at study termination. Pharmacodynamic biomarker changes are also evaluated.
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| Enzyme Assay |
CRBN-binding affinity of the thalidomide-5 component can be measured using surface plasmon resonance (SPR) or fluorescence polarization (FP) competitive binding assays. For SPR, purified CRBN-DDB1 complex is immobilized on a sensor chip, and varying concentrations of the compound are flowed across to determine binding kinetics (kon, koff) and affinity (KD). For FP, a fluorescently labeled thalidomide probe is used in competition with unlabeled test compound to determine IC50 values. Typical assay buffer: 50 mM HEPES (pH 7.4), 150 mM NaCl, 1 mM DTT, 0.01% Tween-20, 0.1 mg/mL BSA. Thalidomide-based CRBN ligands typically exhibit KD values in the low micromolar range (approximately 1-10 uM).
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| Cell Assay |
To construct a PROTAC molecule, the terminal primary amine of this compound is conjugated to a target protein ligand that contains a carboxylic acid group. Standard amide coupling chemistry using HATU or EDCI/HOBt as coupling reagents with DIPEA as base in anhydrous DMF or DMSO is employed. The reaction is typically run for 2-12 hours at room temperature. The resulting PROTAC is purified by preparative HPLC and characterized by LC-MS and NMR. For cellular activity validation, cells are treated with the PROTAC (0.001-10 uM, 4-24 h), followed by lysis and Western blotting to assess target protein degradation. Control conditions include the unconjugated target ligand alone, the CRBN ligand alone, and an inactive control PROTAC (e.g., with a scrambled linker) to confirm on-target degradation.
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| Animal Protocol |
In vivo animal studies with PROTACs incorporating the PEG6 linker follow established xenograft protocols. Female or male immunodeficient mice (nude or NSG, 6-8 weeks old, n=5-10 per group) are implanted subcutaneously with human cancer cells. When tumors reach a volume of approximately 100-200 mm3, animals are randomized into treatment groups. PROTACs are formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline) and administered IP or IV at doses of 1-30 mg/kg. Dosing frequency is typically once daily or every other day for 2-4 weeks. Tumor volumes (calculated as 0.5 × length × width2) and body weights are recorded every 2-3 days. At study endpoint, tumors, plasma, and key tissues are harvested for PK analysis (LC-MS/MS) and PD analysis (Western blot for target protein levels).
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| ADME/Pharmacokinetics |
For the standalone ligand-linker conjugate (molecular weight approximately 574 g/mol), no dedicated pharmacokinetic studies are publicly available. When incorporated into PROTACs, the PEG6 linker contributes moderate hydrophilicity that influences overall molecular properties. PEG6 provides a balance between water solubility and membrane permeability: longer PEG chains improve solubility but can reduce cell permeability, while shorter PEGs may have the opposite effect. PROTACs generally exhibit poor oral bioavailability (typically <10%) due to high molecular weight (>800 Da) and polar surface area, requiring parenteral administration. Plasma half-lives in rodents are typically short to moderate (2-6 hours), with clearance occurring primarily via hepatic metabolism. The hydrochloride salt form enhances solubility for formulation, typically achieving good solubility (>10 mg/mL) in aqueous buffers with appropriate co-solvents.
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| Toxicity/Toxicokinetics |
Toxicology data specific to Thalidomide-5-PEG6-NH2 hydrochloride is not publicly available. As a thalidomide-derived CRBN ligand, the compound shares structural features with thalidomide, which has well-documented teratogenicity (causing severe birth defects) due to its cereblon-binding activity. The PEG6 linker and hydrochloride salt do not eliminate this potential toxicity. Therefore, handling should follow strict chemical safety protocols. All work should be conducted in a well-ventilated chemical fume hood using appropriate personal protective equipment (gloves, lab coat, safety glasses). Pregnant or potentially pregnant individuals should avoid handling thalidomide-derived compounds. This product is for research use only, not for human use or therapeutic applications.
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| Additional Infomation |
Thalidomide-5-PEG6-NH2 hydrochloride is a specialized research tool for PROTAC-based targeted protein degradation studies. Compared to the PEG5 and PEG7 variants, the PEG6 linker offers an intermediate length for optimizing degradation efficiency of specific target proteins. This compound can be connected to the ligand for protein by a linker to form PROTACs. For example, THAL-SNS-032 is a well-known PROTAC constructed using a thalidomide-based CRBN ligand linked to the CDK inhibitor SNS-032. The compound is strictly for research applications including cancer biology, chemical biology, and drug discovery. It has not been evaluated in clinical trials and is not an approved drug. Storage conditions: powder at -20degC for up to 3 years, protected from light and moisture.
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| Molecular Formula |
C25H36CLN3O10
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| Molecular Weight |
574.02
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| Appearance |
White to off-white solid powder
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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 | 1.7421 mL | 8.7105 mL | 17.4210 mL | |
| 5 mM | 0.3484 mL | 1.7421 mL | 3.4842 mL | |
| 10 mM | 0.1742 mL | 0.8710 mL | 1.7421 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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