| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
|
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) component of the E3 ubiquitin ligase complex (as a ligand) and various target proteins via PROTAC-mediated 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].
As a cereblon ligand, this compound retains the immunomodulatory and protein degradation properties of pomalidomide. The PEG5 spacer improves solubility and flexibility for linker conjugation. The amino group enables further derivatization with carboxylic acid-bearing target ligands to form full PROTAC molecules. It facilitates ubiquitination and proteasomal degradation of neo-substrates like Ikaros and Aiolos. |
| ln Vivo |
In vivo degradation activity depends on the specific PROTAC assembled using this building block. Pomalidomide-based PROTACs have shown efficacy in degrading various oncoproteins in mouse xenograft models. The PEG5 linker enhances pharmacokinetic properties by reducing aggregation and improving solubility. Specific in vivo data for this intermediate alone are limited.
|
| Enzyme Assay |
Cereblon binding affinity is measured by fluorescence polarization or SPR using recombinant CRBN-DDB1 complex. Varying concentrations of the compound (0-1000 nM) are incubated with labeled pomalidomide probe in binding buffer. IC50 is calculated from displacement curves. PEGylation does not abolish cereblon binding; the pomalidomide moiety maintains mid-nanomolar affinity (Kd ~1-10 microM).
|
| Cell Assay |
Cells (e.g., MM.1S multiple myeloma or HEK293T) are treated with the compound or its derived PROTAC (1-1000 nM) for 6-24 hours. Target protein degradation is assessed by Western blot. The amino-PEG5-NH2 intermediate alone does not induce degradation unless conjugated to a target binder. It serves as a negative control for PEG linker effects. Cellular toxicity is measured by MTT.
|
| Animal Protocol |
In vivo animal studies are typically performed with the final PROTAC molecule rather than this intermediate alone. For example, PROTACs containing pomalidomide-PEG5 linker are administered to xenograft mice via intraperitoneal or intravenous injection (10-100 mg/kg). Tumor tissues are harvested to assess target degradation by Western blot and immunohistochemistry. Efficacy and pharmacokinetics are evaluated.
|
| ADME/Pharmacokinetics |
The compound has molecular weight of 599.08 g/mol (free base) plus HCl. The PEG5 chain confers increased hydrophilicity and plasma stability. As an intermediate, its pharmacokinetics are not independently characterized. Upon conversion to a PROTAC, the PEG5 linker improves oral bioavailability and reduces plasma protein binding compared to shorter PEG chains.
|
| Toxicity/Toxicokinetics |
The hydrochloride salt form enhances aqueous solubility for formulation. The compound is for research use only and has no approved clinical status. Acute toxicity is expected to be low (LD50 > 1000 mg/kg based on pomalidomide analogs). Standard laboratory safety precautions apply. High concentrations may cause mild irritation.
|
| References | |
| Additional Infomation |
This compound is a key building block for PROTAC synthesis. Pomalidomide is a clinically approved immunomodulatory drug (IMiD) used in multiple myeloma. The amino group allows conjugation to carboxyl-containing warheads via amide bond formation. The PEG5 spacer provides optimal length to bridge the E3 ligase and target protein. No clinical trials exist for this intermediate.
|
| Molecular Formula |
C25H35CLN4O10
|
|---|---|
| Molecular Weight |
587.019206285477
|
| Exact Mass |
586.204
|
| CAS # |
2421217-05-0
|
| Related CAS # |
Pomalidomide-amino-PEG5-NH2;2421217-04-9
|
| PubChem CID |
139035804
|
| Appearance |
Light yellow to yellow solid powder
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
18
|
| Heavy Atom Count |
40
|
| Complexity |
857
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)COCCOCCOCCOCCOCCN.Cl
|
| InChi Key |
VQFIXEMZYHCOIK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C25H34N4O10.ClH/c26-6-7-35-8-9-36-10-11-37-12-13-38-14-15-39-16-21(31)27-18-3-1-2-17-22(18)25(34)29(24(17)33)19-4-5-20(30)28-23(19)32;/h1-3,19H,4-16,26H2,(H,27,31)(H,28,30,32);1H
|
| Chemical Name |
2-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]acetamide;hydrochloride
|
| 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 :~105 mg/mL (~178.87 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7035 mL | 8.5176 mL | 17.0352 mL | |
| 5 mM | 0.3407 mL | 1.7035 mL | 3.4070 mL | |
| 10 mM | 0.1704 mL | 0.8518 mL | 1.7035 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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