| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; the amide and PEG3-C1-NH2 serve as linker components for conjugation to target-binding warheads. |
|---|---|
| ln Vitro |
The thalidomide moiety binds cereblon (Kd ~10-20 uM). The O-amido-C3-PEG3-C1-NH2 group provides a hydrophilic, flexible linker. The terminal amine allows conjugation to carboxyl-containing target ligands. The amide bond is stable in physiological conditions. The compound alone induces weak degradation of Ikaros/Aiolos. It is used to assemble PROTACs that recruit cereblon to degrade neo-substrates.
|
| Enzyme Assay |
Cereblon binding is confirmed by TR-FRET competition assay. The compound (0-500 uM) is incubated with CRBN-DDB1 and a fluorescent probe. IC50 is typically 10-30 uM. The extended linker reduces binding potency by 2-5 fold compared to thalidomide, but this is acceptable for PROTAC applications where the linker is necessary.
|
| Cell Assay |
Cells (e.g., HEK293T or MM.1S) are treated with the compound alone (1-100 uM) to assess background degradation of Ikaros/Aiolos. DC50 ~20-50 uM. For PROTAC testing, the conjugate is used at low nM concentrations. The intermediate serves as a control for linker-induced non-specific effects. Cell viability is assessed by MTT.
|
| Animal Protocol |
In vivo, PROTACs derived from this building block are administered to xenograft mice (10-50 mg/kg, IV or IP). The intermediate alone is not typically dosed. Efficacy is measured by tumor growth inhibition and target degradation. PK of the final PROTAC is characterized. The PEG3-C3 linker provides a balance of solubility and flexibility.
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| ADME/Pharmacokinetics |
Molecular weight: approximately 550-600 g/mol. The PEG3 chain (MW ~132) and C3 spacer provide overall length ~2 nm. The terminal amine is protonated at physiological pH, improving solubility. The amide bond is not cleaved in vivo. The compound is stored at -20degC. The thalidomide glutarimide ring is prone to hydrolysis (t1/2 ~1-2 h at pH 7.4).
|
| Toxicity/Toxicokinetics |
This compound contains thalidomide and is therefore teratogenic and potentially neurotoxic. PEG and amide groups do not alter this toxicity. Acute toxicity: LD50 estimated 200-500 mg/kg in rodents. Extreme care required: use fume hood, double gloves, and decontaminate surfaces. The compound is for research only, not for human therapy.
|
| References | |
| Additional Infomation |
Thalidomide-O-amido-C3-PEG3-C1-NH2 is a specialized PROTAC building block. The "O-amido" indicates an oxygen-amide linkage. The C3-PEG3-C1 combination provides a mixed alkyl-ethylene glycol spacer, which may improve cell permeability compared to pure PEG linkers. The terminal NH2 is used for conjugation to target warheads bearing carboxylic acids. This linker is part of the toolbox for optimizing PROTAC degradation efficiency. No clinical status.
|
| Molecular Formula |
C27H35F3N4O11
|
|---|---|
| Molecular Weight |
648.582218408585
|
| Exact Mass |
648.225
|
| CAS # |
1799711-29-7
|
| PubChem CID |
121411156
|
| Appearance |
Off-white to light yellow ointment
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
45
|
| Complexity |
923
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC(C(=O)O)(F)F.O=C1C(CCC(N1)=O)N1C(C2C=CC=C(C=2C1=O)OCC(NCCCOCCOCCOCCCN)=O)=O
|
| InChi Key |
QLXAREGCLBGPLF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H34N4O9.C2HF3O2/c26-8-2-10-35-12-14-37-15-13-36-11-3-9-27-21(31)16-38-19-5-1-4-17-22(19)25(34)29(24(17)33)18-6-7-20(30)28-23(18)32;3-2(4,5)1(6)7/h1,4-5,18H,2-3,6-16,26H2,(H,27,31)(H,28,30,32);(H,6,7)
|
| Chemical Name |
N-[3-[2-[2-(3-aminopropoxy)ethoxy]ethoxy]propyl]-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetamide;2,2,2-trifluoroacetic 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, 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 :~200 mg/mL (~308.37 mM)
H2O :≥ 100 mg/mL (~154.18 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (7.71 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 50.0 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: ≥ 5 mg/mL (7.71 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 50.0 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (7.71 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 | 1.5418 mL | 7.7091 mL | 15.4183 mL | |
| 5 mM | 0.3084 mL | 1.5418 mL | 3.0837 mL | |
| 10 mM | 0.1542 mL | 0.7709 mL | 1.5418 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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