| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; also targets Ikaros (IKZF1) and Aiolos (IKZF3) for proteasomal degradation. |
|---|---|
| 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].
Thalidomide binds cereblon with moderate affinity (Kd ~10-20 uM). The PEG5 linker provides high water solubility and flexibility (length ~2.5 nm). The terminal COOH can be activated to NHS ester or coupled directly to amines using EDC/NHS chemistry. The compound alone induces weak degradation of Ikaros/Aiolos. In PROTACs, it serves as the E3 ligase recruiting moiety. Compared to PEG4, PEG5 may improve solubility further. |
| Enzyme Assay |
Cereblon binding is measured by TR-FRET or SPR. Recombinant CRBN-DDB1 is incubated with a fluorescent probe and thalidomide-PEG5-COOH (0-500 uM). IC50 is typically 5-20 uM. The PEG5-COOH group does not significantly alter binding compared to thalidomide. For PROTACs, the carboxylic acid is first activated before conjugation to an amine-containing warhead.
|
| Cell Assay |
The compound alone (1-100 uM) is tested in MM.1S cells for Ikaros degradation by Western blot. DC50 ~10-30 uM, similar to thalidomide. The PEG5 chain does not prevent cellular uptake. For PROTAC evaluation, the conjugate is used at lower concentrations (1-1000 nM). The intermediate is used as a negative control or to assess linker effects.
|
| Animal Protocol |
PROTACs assembled from thalidomide-PEG5-COOH are administered to xenograft mice (10-50 mg/kg, IV). Tumor tissues are analyzed for target degradation. The intermediate alone may be dosed as a control at high doses (50-100 mg/kg) but shows minimal efficacy. PK parameters of the final PROTAC depend on the warhead.
|
| ADME/Pharmacokinetics |
Molecular weight: approximately 530 g/mol. PEG5 chain (MW ~220) provides high aqueous solubility (>10 mg/mL). The carboxylic acid has pKa ~4.5. The compound is stable at -20degC. In physiological buffers, the thalidomide glutarimide ring undergoes hydrolysis (t1/2 ~1-2 hours at pH 7.4, 37degC). The COOH remains stable.
|
| Toxicity/Toxicokinetics |
Thalidomide derivatives are teratogenic and potentially neurotoxic. PEG5-COOH does not reduce this risk. Acute toxicity: LD50 likely similar to thalidomide (200-500 mg/kg in rodents). Handle with extreme precautions: double gloves, ventilated fume hood. Do not use if pregnant. The compound is for research only.
|
| References | |
| Additional Infomation |
Thalidomide-PEG5-COOH is a PROTAC building block. The PEG5 linker provides a hydrophilic spacer that reduces aggregation and improves pharmacokinetics of the final PROTAC compared to alkyl linkers. The COOH terminus allows standard amide coupling. Thalidomide-based PROTACs are widely used for targeted protein degradation. This compound has no clinical approval but is a research tool. Compare to lenalidomide- and pomalidomide-based linkers, which have higher cereblon affinity.
|
| Molecular Formula |
C24H30N2O11
|
|---|---|
| Molecular Weight |
522.501807689667
|
| Exact Mass |
522.184
|
| CAS # |
2688100-28-7
|
| PubChem CID |
162642706
|
| Appearance |
Light yellow to brown ointment
|
| LogP |
-0.8
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
37
|
| Complexity |
821
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C(CCC(N1)=O)N1C(C2C=CC(=CC=2C1=O)OCCOCCOCCOCCOCCC(=O)O)=O
|
| InChi Key |
GORYVJWAUFWGOR-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H30N2O11/c27-20-4-3-19(22(30)25-20)26-23(31)17-2-1-16(15-18(17)24(26)32)37-14-13-36-12-11-35-10-9-34-8-7-33-6-5-21(28)29/h1-2,15,19H,3-14H2,(H,28,29)(H,25,27,30)
|
| Chemical Name |
3-[2-[2-[2-[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]oxyethoxy]ethoxy]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 :~50 mg/mL (~95.69 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.98 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 20.8 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: ≥ 2.08 mg/mL (3.98 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 | 1.9139 mL | 9.5694 mL | 19.1388 mL | |
| 5 mM | 0.3828 mL | 1.9139 mL | 3.8278 mL | |
| 10 mM | 0.1914 mL | 0.9569 mL | 1.9139 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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