| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
The compound targets cereblon (CRBN), an E3 ubiquitin ligase substrate receptor component of the CUL4-RBX1-DDB1-CRBN complex. The thalidomide-derived moiety binds to CRBN, recruiting the E3 ligase machinery. When this CRBN ligand is conjugated to a target protein ligand via the PEG7 linker, the resulting PROTAC molecule brings the target protein into proximity with the E3 ligase, leading to target ubiquitination and subsequent proteasomal degradation. The long, hydrophilic PEG7 linker enhances water solubility and provides flexibility, which may be optimal for targets requiring significant spatial separation from CRBN.
|
|---|---|
| ln Vitro |
In vitro activity of this compound is realized through its use as a PROTAC building block. When conjugated to a target protein-binding ligand, the resulting PROTAC induces target protein ubiquitination and proteasome-dependent degradation. The ligand-linker conjugate itself exhibits minimal standalone biological activity. In cell-based assays, PROTACs constructed with this linker (such as THAL-SNS-032) have been shown to effectively degrade target proteins at nanomolar concentrations. For example, THAL-SNS-032, a PROTAC targeting CDK9, demonstrates potent degradation of CDK9 in cancer cell lines, leading to reduced cell proliferation and increased apoptosis. Western blot analysis typically shows concentration-dependent target protein reduction with DC50 values in the low nanomolar range after 4-24 hour treatments.
|
| ln Vivo |
In vivo efficacy studies with PROTACs incorporating the PEG7 linker are typically conducted in murine xenograft models. Complete PROTAC molecules are administered to tumor-bearing mice via intraperitoneal (IP) or intravenous (IV) routes at doses typically ranging from 1-30 mg/kg, often on a daily or every-other-day schedule for 2-4 weeks. The hydrophilic PEG7 linker improves water solubility, facilitating formulation for in vivo administration. Efficacy is assessed by tumor volume measurements, Western blot analysis of target protein degradation in harvested tumor tissues, and evaluation of pharmacodynamic biomarkers. The PEG7 linker may also reduce non-specific protein binding and improve in vivo tolerability compared to highly hydrophobic linkers.
|
| Enzyme Assay |
CRBN-binding affinity of the thalidomide-5 component can be measured using fluorescence polarization (FP) competitive binding assays or surface plasmon resonance (SPR). Purified CRBN-DDB1 complex is incubated with a fluorescent thalidomide probe and varying concentrations of the test compound. Binding affinity (IC50 or KD) is determined by measuring probe displacement. Typical assay conditions: 50 mM HEPES (pH 7.5), 150 mM NaCl, 1 mM DTT, 0.01% Tween-20, 0.1 mg/mL BSA. Thalidomide-based CRBN ligands generally exhibit KD values in the low micromolar range. The PEG7 linker attached at the 5-position does not interfere with the CRBN binding interface, as this position is a known site for linker attachment in PROTAC design.
|
| Cell Assay |
To construct a PROTAC, the terminal primary amine of this compound is conjugated to a target protein ligand bearing a carboxylic acid group via standard amide coupling using HATU (or EDCI/HOBt) and DIPEA in DMF or DMSO. The resulting PROTAC is purified by preparative HPLC and characterized by LC-MS. For cell-based activity assays, cultured cells are treated with the PROTAC at concentrations ranging from 0.001-10 uM for 4-24 hours, then lysed. Target protein levels are assessed by Western blotting. Dose-response curves are generated to determine DC50 (concentration causing 50% degradation) and Dmax (maximal degradation efficiency). Control treatments include the unconjugated target ligand alone and the CRBN ligand alone.
|
| Animal Protocol |
In vivo animal studies with PROTACs containing this PEG7 linker follow standard xenograft protocols. Female or male immunodeficient mice (6-8 weeks old, n=5-10 per group) bearing subcutaneous human tumor xenografts are randomized into treatment groups. PROTACs are formulated in vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline) and administered IP or IV at 1-30 mg/kg. Dosing frequency typically ranges from once daily to three times weekly. Tumor volumes (measured by calipers) and body weights are recorded every 2-3 days. At study termination (typically after 2-4 weeks), tumors and plasma are collected for Western blot analysis to confirm target degradation and for LC-MS/MS PK analysis.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of PROTACs incorporating this PEG7 linker vary with the attached target ligand, but several generalizations apply. The PEG7 linker (7 ethylene oxide units, molecular weight ~308 Da contributed by the PEG chain) is highly hydrophilic, which generally improves aqueous solubility and reduces plasma protein binding compared to alkyl linkers. However, high hydrophilicity can also reduce cell membrane permeability, potentially limiting oral absorption. PROTACs containing long PEG linkers typically exhibit poor oral bioavailability and are usually administered parenterally. Plasma half-lives in rodents are often short (1-6 hours) due to rapid clearance. The hydrochloride salt form enhances solubility for formulation, typically achieving >10 mg/mL solubility in aqueous buffers.
|
| Toxicity/Toxicokinetics |
For the standalone ligand-linker conjugate (molecular weight approximately 618 g/mol), no dedicated toxicity studies are available. As a thalidomide-derived compound, it shares structural features with thalidomide, which has well-documented teratogenic effects. The hydrochloride salt requires standard chemical safety precautions. Researchers should handle thalidomide-derived compounds with particular caution regarding potential developmental toxicity; pregnant or potentially pregnant individuals should avoid direct handling. Trifluoroacetic acid, if present, is corrosive. All work should be conducted in a chemical fume hood with appropriate personal protective equipment (gloves, lab coat, safety glasses). This compound is for research use only and is not approved for human or therapeutic use.
|
| Additional Infomation |
Thalidomide-5-PEG7-NH2 hydrochloride is a key building block in PROTAC technology for targeted protein degradation. It is classified as an immunomodulatory drug and small molecule compound with recognized anti-inflammatory and anti-cancer properties when incorporated into PROTACs. The compound can be connected to the ligand for protein by a linker to form PROTACs. For example, THAL-SNS-032 is a well-characterized PROTAC constructed using a thalidomide-based CRBN ligand linked to the CDK inhibitor SNS-032. This product is strictly for research use only-not for human use, therapeutic applications, or diagnostic purposes. The compound should be stored at -20degC, protected from light and moisture, under inert atmosphere.
|
| Molecular Formula |
C27H40CLN3O11
|
|---|---|
| Molecular Weight |
618.07
|
| Appearance |
White to off-white solid powder
|
| 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 | 1.6179 mL | 8.0897 mL | 16.1794 mL | |
| 5 mM | 0.3236 mL | 1.6179 mL | 3.2359 mL | |
| 10 mM | 0.1618 mL | 0.8090 mL | 1.6179 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
Copyright 2020 InvivoChem LLC | All Rights Reserved
