| Size | Price | |
|---|---|---|
| 50mg | ||
| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; the propargyl group enables CuAAC conjugation to azide-containing warheads; the PEG3 spacer provides hydrophilicity. |
|---|---|
| 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 (Kd ~10-20 uM). The propargyl group allows bioorthogonal conjugation via click chemistry. The PEG3 spacer (3 ethylene glycol units, MW ~132, length ~1.2 nm) provides increased solubility and flexibility compared to PEG1. The terminal COOH can also be used for standard amide coupling. The compound alone induces weak degradation of Ikaros/Aiolos (DC50 ~20-50 uM). In PROTACs, it serves as the E3 ligase recruiter. |
| Enzyme Assay |
Cereblon binding is confirmed by TR-FRET. Thalidomide-propargyne-PEG3-COOH (0-500 uM) is tested in competition assays. IC50 typically 10-30 uM. The longer PEG3 spacer reduces binding slightly more than PEG1, but the difference is minor. Click reaction efficiency with an azide model compound is verified by LC-MS (usually >80% conversion).
|
| 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 evaluation, the compound is conjugated to an azide-tagged target warhead via CuAAC. The purified PROTAC (1-1000 nM) is tested for degradation of the target protein by Western blot. The intermediate serves as a clickable handle control.
|
| Animal Protocol |
In vivo, PROTACs derived from this building block are dosed in xenograft mice (10-50 mg/kg, IV). The click conjugation is done ex vivo. Tumor tissues are harvested to measure target degradation by Western blot and IHC. PK parameters (t1/2, Cmax, AUC) are determined for the final PROTAC. The PEG3 spacer may improve plasma stability compared to PEG1.
|
| ADME/Pharmacokinetics |
Molecular weight: approximately 520-570 g/mol. PEG3 chain (MW ~132) provides water solubility >10 mg/mL. The propargyl group is stable. The COOH group (pKa ~4.5) can be used for amide coupling. The compound is stored at -20degC. The thalidomide glutarimide ring hydrolyzes in buffer (t1/2 ~1-2 h at pH 7.4). The PEG3 spacer does not prevent hydrolysis.
|
| Toxicity/Toxicokinetics |
Thalidomide derivatives are teratogenic and neurotoxic. Propargyl-PEG3-COOH does not reduce this risk. Acute toxicity: LD50 estimated 200-500 mg/kg in rodents. Extreme caution required: fume hood, double gloves. Not for human use. The compound is for research only. Standard chemical safety protocols apply.
|
| References | |
| Additional Infomation |
This PROTAC building block combines a propargyl click-handle with a PEG3 spacer, offering better solubility and flexibility than shorter PEG versions. The PEG3 length is often optimal for ternary complex formation. The COOH provides an alternative conjugation site. Click chemistry allows rapid and modular PROTAC synthesis without protecting group manipulations. This compound is a research tool for targeted protein degradation. No clinical approval.
|
| Molecular Formula |
C23H24N2O9
|
|---|---|
| Molecular Weight |
472.444666862488
|
| Exact Mass |
472.148
|
| CAS # |
2797649-54-6
|
| PubChem CID |
162642709
|
| Appearance |
Light yellow to yellow viscous liquid
|
| LogP |
-0.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
34
|
| Complexity |
874
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C(CCC(N1)=O)N1C(C2C=CC(C#CCOCCOCCOCCC(=O)O)=CC=2C1=O)=O
|
| InChi Key |
WWIBTSXCGDRYOX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H24N2O9/c26-19-6-5-18(21(29)24-19)25-22(30)16-4-3-15(14-17(16)23(25)31)2-1-8-32-10-12-34-13-11-33-9-7-20(27)28/h3-4,14,18H,5-13H2,(H,27,28)(H,24,26,29)
|
| Chemical Name |
3-[2-[2-[3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]prop-2-ynoxy]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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 :~100 mg/mL (~211.67 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.29 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 25.0 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: ≥ 2.5 mg/mL (5.29 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 25.0 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 | 2.1167 mL | 10.5834 mL | 21.1667 mL | |
| 5 mM | 0.4233 mL | 2.1167 mL | 4.2333 mL | |
| 10 mM | 0.2117 mL | 1.0583 mL | 2.1167 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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