| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; the propargyl group enables copper-catalyzed azide-alkyne cycloaddition (CuAAC) for conjugation. |
|---|---|
| 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 (terminal alkyne) group allows efficient conjugation to azide-functionalized target ligands via click chemistry. The PEG1 spacer (single ethylene glycol unit) provides a minimal hydrophilic linker. The COOH group offers an alternative conjugation handle (amide coupling). The compound alone induces weak degradation of Ikaros/Aiolos. The propargyl group is stable and bioorthogonal. |
| Enzyme Assay |
Cereblon binding is measured by TR-FRET. Thalidomide-propargyne-PEG1-COOH (0-500 uM) competes with a probe. IC50 ~10-30 uM. The propargyl-PEG1-COOH group reduces affinity by 2-5 fold but remains useful. The compound can also be tested in a click chemistry reaction with an azide-containing molecule to confirm conjugation efficiency by LC-MS.
|
| Cell Assay |
Cells (e.g., MM.1S) are treated with the compound alone (1-100 uM) to assess background Ikaros degradation (DC50 ~20-50 uM). For PROTAC generation, the compound is first conjugated to an azide-tagged warhead via CuAAC. The resulting PROTAC is tested at 1-1000 nM for target degradation by Western blot. The intermediate serves as a clickable handle.
|
| Animal Protocol |
PROTACs assembled via click chemistry using this building block are administered to xenograft mice (10-50 mg/kg, IV). The click reaction is performed in vitro before dosing. In vivo efficacy is evaluated by tumor growth inhibition and target degradation. The intermediate alone is not dosed. PK depends on the final conjugate.
|
| ADME/Pharmacokinetics |
Molecular weight: approximately 400-450 g/mol. Propargyl group (C≡CH) has MW ~25. PEG1 (MW ~44) plus COOH. The compound is soluble in DMSO and partially in water. The alkyne is stable at -20degC. The thalidomide glutarimide ring hydrolyzes in aqueous medium (t1/2 ~1-2 h). The propargyl group can participate in click reactions at room temperature.
|
| Toxicity/Toxicokinetics |
Thalidomide derivatives are teratogenic and neurotoxic. Propargyl group is flammable but not highly toxic. The compound requires extreme care due to thalidomide core. Acute toxicity: LD50 estimated 200-500 mg/kg. Use fume hood, double gloves, and dedicated equipment. Not for human use. The compound is for research only.
|
| References | |
| Additional Infomation |
This PROTAC building block features a propargyl group for click chemistry, offering an orthogonal conjugation method compared to traditional amide coupling. The PEG1 spacer provides minimal separation between thalidomide and the alkyne. The COOH group allows conventional conjugation as an alternative. Click chemistry is advantageous for modular assembly of PROTAC libraries. This compound is used in research to expedite PROTAC synthesis. No clinical approval.
|
| Molecular Formula |
C19H16N2O7
|
|---|---|
| Molecular Weight |
384.339545249939
|
| Exact Mass |
384.095
|
| CAS # |
2828438-36-2
|
| PubChem CID |
146485051
|
| Appearance |
White to yellow solid powder
|
| LogP |
-0.1
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
28
|
| Complexity |
778
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C=C(C=C3)C#CCOCCC(=O)O
|
| InChi Key |
HVNLXJHGBVADJO-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H16N2O7/c22-15-6-5-14(17(25)20-15)21-18(26)12-4-3-11(10-13(12)19(21)27)2-1-8-28-9-7-16(23)24/h3-4,10,14H,5-9H2,(H,23,24)(H,20,22,25)
|
| Chemical Name |
3-[3-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]prop-2-ynoxy]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 :~125 mg/mL (~325.23 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.41 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 (5.41 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 (5.41 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 | 2.6019 mL | 13.0093 mL | 26.0186 mL | |
| 5 mM | 0.5204 mL | 2.6019 mL | 5.2037 mL | |
| 10 mM | 0.2602 mL | 1.3009 mL | 2.6019 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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