| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Cereblon
CRBN (cereblon), an E3 ubiquitin ligase. |
|---|---|
| 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[2].
As a cereblon-binding ligand-linker conjugate, Glutarimide-Isoindolinone-NH-PEG2-COOH 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 PEG2 linker provides a very short, hydrophilic, and flexible connection, which can be optimal for target proteins where the E3 ligase recruitment site is very close to the target protein binding site. The glutarimide-isoindolinone scaffold is a known cereblon-binding moiety with structural similarity to Thalidomide and Pomalidomide. |
| 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 ≥98%. 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).
|
| 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 very short PEG2 spacer may be critical for achieving degradation activity for target proteins with closely spaced binding sites.
|
| 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 very short PEG2 spacer may result in a small, compact PROTAC that can penetrate tissues more effectively.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of 419.43, a molecular formula of C20H25N3O7, and a standard purity of ≥98%. It appears as an ointment (yellow to brown). For storage, it should be kept as an ointment at -20degC for up to 3 years or in a solvent at -80degC for 6 months. It is soluble in DMSO. The product should be stored in a sealed container, away from moisture, and protected from light. The IUPAC name is 3-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)amino)ethoxy)ethoxy)propanoic acid. CAS: 2803827-03-2.
|
| 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. It is a PROTAC building block for research and development purposes only.
|
| References | |
| Additional Infomation |
The PEG2 linker is the shortest PEG linker commonly used in PROTAC design, providing a minimal hydrophilic spacer of only two ethylene glycol units. This very short linker can be critical for achieving degradation activity for target-E3 ligase pairs where a longer linker would prevent the formation of a productive ternary complex due to excessive flexibility or steric hindrance. The glutarimide-isoindolinone scaffold is a cereblon-binding motif that is structurally similar to the clinically approved immunomodulatory imide drugs. This conjugate provides a functionalized cereblon ligand with a very short PEG2 linker and a terminal carboxylic acid, enabling direct conjugation to target protein ligands via standard amide coupling. This compound is also known as Glutarimide-Isoindolinone-NH-PEG2-COOH and is a valuable building block for developing cereblon-recruiting PROTACs with minimal linker lengths.
|
| Molecular Formula |
C20H25N3O7
|
|---|---|
| Molecular Weight |
419.43
|
| Exact Mass |
419.169
|
| CAS # |
2803827-03-2
|
| PubChem CID |
162642720
|
| Appearance |
Yellow to brown ointment
|
| LogP |
-0.6
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
30
|
| Complexity |
656
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(O)(=O)CCOCCOCCNC1C=CC2=C(C=1)CN(C1CCC(=O)NC1=O)C2=O
|
| InChi Key |
OLXWGGOWRQJBRT-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H25N3O7/c24-17-4-3-16(19(27)22-17)23-12-13-11-14(1-2-15(13)20(23)28)21-6-8-30-10-9-29-7-5-18(25)26/h1-2,11,16,21H,3-10,12H2,(H,25,26)(H,22,24,27)
|
| Chemical Name |
3-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]amino]ethoxy]ethoxy]propanoic acid
|
| 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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO :~73.33 mg/mL (~174.83 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.75 mg/mL (16.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 67.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 6.75 mg/mL (16.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 67.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 5.5 mg/mL (13.11 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3842 mL | 11.9209 mL | 23.8419 mL | |
| 5 mM | 0.4768 mL | 2.3842 mL | 4.7684 mL | |
| 10 mM | 0.2384 mL | 1.1921 mL | 2.3842 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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