| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Cereblon
CRBN (cereblon), an E3 ubiquitin ligase. |
|---|---|
| ln Vitro |
The E3 ubiquitin ligase ligand and the target protein ligand are the two distinct ligands found in PROTAC, which are joined by a linker. Specifically, target proteins are degraded by PROTAC through the intracellular ubiquitin-proteasome system [1].
As a cereblon-binding ligand-linker conjugate, Pomalidomide 4'-PEG5-acid itself has no intrinsic biological activity; its function is to recruit the E3 ubiquitin ligase complex. The terminal carboxylic acid is conjugated to a target protein ligand via amide bond formation using standard coupling reagents (e.g., EDC, HATU). The resulting PROTAC can simultaneously bind to both a target protein and cereblon, leading to ubiquitination and subsequent proteasomal degradation of the target protein. The PEG5 linker provides a long, hydrophilic, and flexible spacer that can be optimal for target proteins with binding sites that are far from the cereblon recruitment site. The PEG5 linker significantly enhances the water solubility of the final PROTAC, which is often a challenge for PROTAC molecules. |
| ln Vivo |
No specific in vivo activity has been reported for this conjugate alone; its in vivo degradation activity is observed only when conjugated to a target protein ligand to form a complete PROTAC molecule. The in vivo efficacy of such a PROTAC is typically evaluated in animal models of target-driven diseases.
|
| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. As a synthetic intermediate, its quality is confirmed by analytical methods such as HPLC and NMR, with a standard purity of ≥95%. Its binding affinity to cereblon is validated as part of a complete PROTAC construct using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The PEG5 linker can be characterized by mass spectrometry. The IUPAC name is 3-(2-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)ethoxy)ethoxy)propanoic acid.
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| Cell Assay |
N/A; this conjugate is not tested alone in cell-based assays but is used as a building block for constructing PROTACs. In a typical conjugation step, the terminal carboxylic acid is activated with EDC and NHS and reacted with a primary amine-containing target protein ligand. The resulting PROTAC is then tested in target-expressing cancer cells for degradation activity by Western blotting to determine the DC50 (half-maximal degradation concentration). The long PEG5 linker is expected to significantly improve the aqueous solubility of the final PROTAC, which may enhance cellular uptake and target engagement.
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| Animal Protocol |
N/A; no animal studies are performed with the ligand-linker conjugate alone. For in vivo studies of a complete PROTAC, the molecule is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered to animal models via intraperitoneal (IP) or intravenous (IV) injection. Target degradation in tissues and tumor growth inhibition are monitored. The long PEG5 spacer may improve the pharmacokinetic properties of the conjugate by enhancing water solubility and reducing aggregation, potentially leading to improved in vivo efficacy.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of approximately 565.58, a molecular formula of C26H35N3O11, and a standard purity of ≥95%. For storage, it should be kept as a solid at -20degC for up to 3 years, sealed, away from moisture. It is soluble in DMSO. The product should be stored in a sealed container under an inert atmosphere. CAS: 2139348-63-1.
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or veterinary use. Standard chemical safety precautions should be followed during handling. The product is stable under recommended storage conditions. It is not an approved therapeutic drug and has not been cleared for clinical use. Pomalidomide is an immunomodulatory drug (IMiD) clinically used for multiple myeloma; this derivative is for research purposes only. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license.
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| References | |
| Additional Infomation |
The 5-unit PEG linker (PEG5) provides a long, hydrophilic, and flexible spacer that can be optimal for target-E3 ligase pairs that require a longer distance between binding sites. The PEG5 linker also significantly improves the water solubility of the final PROTAC, addressing a common challenge in PROTAC development. This conjugate is a valuable building block for developing cereblon-recruiting PROTACs with optimized linker lengths for specific target proteins. The terminal carboxylic acid enables direct conjugation to target protein ligands via standard amide coupling. This compound is also known as Pomalidomide-PEG5-CO2H and is widely used in targeted protein degradation research.
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| Molecular Formula |
C26H35N3O11
|
|---|---|
| Molecular Weight |
565.569607973099
|
| Exact Mass |
565.227
|
| CAS # |
2139348-63-1
|
| PubChem CID |
132020460
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| Appearance |
White to yellow solid-liquid Mixture
|
| LogP |
-0.4
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
40
|
| Complexity |
871
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C(CCC(N1)=O)N1C(C2C=CC=C(C=2C1=O)NCCOCCOCCOCCOCCOCCC(=O)O)=O
|
| InChi Key |
PMCQLKMOQUEEDR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H35N3O11/c30-21-5-4-20(24(33)28-21)29-25(34)18-2-1-3-19(23(18)26(29)35)27-7-9-37-11-13-39-15-17-40-16-14-38-12-10-36-8-6-22(31)32/h1-3,20,27H,4-17H2,(H,31,32)(H,28,30,33)
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| Chemical Name |
3-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid
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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. |
| 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) |
H2O :~50 mg/mL (~88.41 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 | 1.7681 mL | 8.8406 mL | 17.6813 mL | |
| 5 mM | 0.3536 mL | 1.7681 mL | 3.5363 mL | |
| 10 mM | 0.1768 mL | 0.8841 mL | 1.7681 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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