| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| 500mg |
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| 1g |
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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, Thalidomide-NH-CH2-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 methylene (CH2) linker is the shortest possible spacer, providing a rigid, minimal connection between the thalidomide core and the conjugated ligand. This minimal spacer can be optimal for target proteins where the E3 ligase recruitment site is very close to the target protein binding site. This conjugate has been used to form THAL-SNS-032, a PROTAC targeting cyclin-dependent kinases (CDKs). |
| 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). The IUPAC name is 2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetic acid.
|
| 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 extremely short methylene linker may be critical for achieving degradation activity for certain target proteins where longer linkers are ineffective.
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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 minimal methylene linker results in a compact PROTAC that may have improved tissue penetration.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of 331.28, a molecular formula of C15H13N3O6, and a standard purity of ≥98%. The IUPAC name is 2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetic acid. It appears as a solid. For storage, it should be kept as a powder at -20degC for up to 3 years or at 4degC for up to 2 years, sealed, away from moisture. In a solvent, it can be stored at -80degC for 6 months or at -20degC for 1 month. It is soluble in DMSO. CAS: 927670-97-1.
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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. Thalidomide is an immunomodulatory drug with known teratogenic effects; this derivative is for research purposes only.
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| References | |
| Additional Infomation |
The methylene (CH2) linker is the shortest possible spacer between the thalidomide core and the terminal carboxylic acid, providing a rigid, minimal connection that is ideal for target-E3 ligase pairs that require a very short distance between binding sites for ternary complex formation. This conjugate has been used to construct THAL-SNS-032, a potent PROTAC degrader of CDK4, CDK6, and CDK9. The minimal linker design may contribute to the high degradation potency and selectivity of this PROTAC. This compound is also known as (2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)glycine and is a valuable building block for developing cereblon-recruiting PROTACs with minimal linker lengths.
|
| Molecular Formula |
C15H13N3O6
|
|---|---|
| Molecular Weight |
331.28
|
| Exact Mass |
331.08
|
| CAS # |
927670-97-1
|
| PubChem CID |
58827328
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| Appearance |
Solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
713.9±60.0 °C at 760 mmHg
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| Flash Point |
385.6±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
|
| Index of Refraction |
1.700
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| LogP |
-1.06
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
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| Heavy Atom Count |
24
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| Complexity |
618
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CNC1C2=C(C(N(C3CCC(=O)NC3=O)C2=O)=O)C=CC=1)O
|
| InChi Key |
LRGLFYOYKPSPJQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13N3O6/c19-10-5-4-9(13(22)17-10)18-14(23)7-2-1-3-8(12(7)15(18)24)16-6-11(20)21/h1-3,9,16H,4-6H2,(H,20,21)(H,17,19,22)
|
| Chemical Name |
2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetic 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 |
| 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 :~50 mg/mL (~150.93 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (5.04 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.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (5.04 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 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0186 mL | 15.0930 mL | 30.1859 mL | |
| 5 mM | 0.6037 mL | 3.0186 mL | 6.0372 mL | |
| 10 mM | 0.3019 mL | 1.5093 mL | 3.0186 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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