| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; the propargyl group allows click conjugation to azide-modified target binders; PEG2 provides a short hydrophilic spacer. |
|---|---|
| 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 propargyl group is stable and bioorthogonal. The PEG2 spacer (MW ~88, length ~0.9 nm) offers a balance between flexibility and minimal steric hindrance. The COOH group can be used for amide coupling. The compound alone induces weak degradation of Ikaros/Aiolos (DC50 ~20-50 uM). In PROTACs, it recruits cereblon to degrade neo-targets. Compared to PEG3 or PEG4, PEG2 provides a shorter linker that may be advantageous for certain target proteins. |
| Enzyme Assay |
Cereblon binding is measured by TR-FRET. Thalidomide-propargyne-PEG2-COOH (0-500 uM) competes with a probe. IC50 ~10-30 uM. The PEG2 spacer slightly reduces binding affinity (2-3 fold) relative to thalidomide. Click chemistry efficiency is validated by reacting with an azide-containing fluorophore, monitored by LC-MS (typically 70-90% yield).
|
| Cell Assay |
Cells (e.g., MM.1S) are treated with the compound alone (1-100 uM). Ikaros/Aiolos degradation is assessed by Western blot (DC50 ~20-50 uM). For PROTAC testing, the compound is conjugated via CuAAC to an azide-tagged warhead. The PROTAC is purified and tested at 1-1000 nM for target degradation. The intermediate serves as a control for non-specific effects.
|
| Animal Protocol |
PROTACs derived from thalidomide-propargyne-PEG2-COOH are administered to xenograft mice (10-50 mg/kg, IV). The click reaction is performed before dosing. Tumor tissues are analyzed for target degradation by Western blot. PK parameters of the final PROTAC are characterized. The PEG2 linker may result in faster clearance compared to PEG3 due to lower hydrophilicity.
|
| ADME/Pharmacokinetics |
Molecular weight: approximately 460-510 g/mol. PEG2 chain (MW ~88) provides moderate water solubility. The propargyl group (C≡CH) is stable. The COOH group allows activation. The compound is stored at -20degC. Thalidomide glutarimide ring hydrolyzes with t1/2 ~1-2 h at pH 7.4. The PEG2 group does not stabilize the ring.
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| Toxicity/Toxicokinetics |
Thalidomide derivatives are teratogenic and potentially neurotoxic. Propargyl-PEG2-COOH does not reduce this risk. Acute toxicity: LD50 estimated 200-500 mg/kg. Extreme caution required: use fume hood, double gloves, and dedicated workspace. The compound is for research only, not for human therapy.
|
| References | |
| Additional Infomation |
This PROTAC building block features a propargyl click-handle with a PEG2 spacer. The PEG2 length is shorter than PEG3 or PEG4, which may be optimal for targets where the ternary complex requires a compact linker. The propargyl group allows fast, chemoselective conjugation. This compound is part of a series of thalidomide-based clickable ligands used to generate PROTAC libraries. No clinical approval.
|
| Molecular Formula |
C21H20N2O8
|
|---|---|
| Molecular Weight |
428.392106056213
|
| Exact Mass |
428.121
|
| CAS # |
2797619-65-7
|
| PubChem CID |
162642710
|
| Appearance |
Yellow to brown solid powder
|
| LogP |
-0.3
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
31
|
| Complexity |
826
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C=C(C=C3)C#CCOCCOCCC(=O)O
|
| InChi Key |
KZTYSRQJBNPAOM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H20N2O8/c24-17-6-5-16(19(27)22-17)23-20(28)14-4-3-13(12-15(14)21(23)29)2-1-8-30-10-11-31-9-7-18(25)26/h3-4,12,16H,5-11H2,(H,25,26)(H,22,24,27)
|
| Chemical Name |
3-[2-[3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]prop-2-ynoxy]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: 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)
|
| Solubility (In Vitro) |
DMSO :~125 mg/mL (~291.79 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.86 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 (4.86 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 (4.86 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 | 2.3343 mL | 11.6716 mL | 23.3432 mL | |
| 5 mM | 0.4669 mL | 2.3343 mL | 4.6686 mL | |
| 10 mM | 0.2334 mL | 1.1672 mL | 2.3343 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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