| Size | Price | |
|---|---|---|
| 50mg | ||
| Other Sizes |
| Targets |
The pomalidomide moiety binds to cereblon (CRBN), a substrate receptor of the CRL4 E3 ubiquitin ligase complex. This compound recruits CRBN to ubiquitinate target proteins that are brought into proximity via a target-binding ligand attached through click chemistry conjugation.
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|---|---|
| ln Vitro |
PROTAC molecules synthesized from this building block induce degradation of target proteins (e.g., BRD4, BTK) with DC₅0 values in the nanomolar to low micromolar range. The efficacy depends on the target protein, linker length, and cell line. Degradation is confirmed by Western blot.
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| ln Vivo |
In vivo, PROTACs derived from this compound have been shown to degrade oncogenic proteins in mouse xenograft models, leading to inhibition of tumor growth and reduced target protein levels in tissues. The compound itself is not administered alone; it is incorporated into complete PROTAC molecules.
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| Enzyme Assay |
Non-cell assays use purified CRBN-DDB1 complex and a fluorescence polarization (FP) or TR-FRET assay to measure binding affinity. The pomalidomide moiety binds to CRBN, and displacement of a fluorescent probe is measured. The IC₅0 is typically in the sub-micromolar range for the cereblon interaction.
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| Cell Assay |
For cell studies, the complete PROTAC conjugate (synthesized from this building block) is added to cell culture medium (0.1-10 uM). Target protein degradation is assessed by Western blot after 4-24 hours. Cell viability is measured by CellTiter-Glo or MTT assay. Off-target degradation can be assessed by proteomics.
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| Animal Protocol |
In animal experiments, PROTAC molecules containing this building block are typically administered to mice with tumor xenografts by intraperitoneal injection (10-50 mg/kg, daily or every other day). Tumors are harvested to measure target protein levels by Western blot or IHC. Tumor volume is measured twice weekly.
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| ADME/Pharmacokinetics |
The pharmacokinetics of PROTACs containing this building block are variable and depend on the target-binding ligand. The PEG3 linker enhances aqueous solubility. The terminal azide is chemically stable under physiological conditions. The pomalidomide core has moderate metabolic stability, with half-lives typically 1-4 hours in rodents.
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| Toxicity/Toxicokinetics |
The pomalidomide scaffold can cause myelosuppression, teratogenicity, and dose-limiting toxicities at high systemic exposures. The linker and terminal azide do not contribute significantly to toxicity. Complete PROTAC molecules should be evaluated individually for their safety profiles in vivo.
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| References |
[1]. Dawid Drelinkiewicz, et al. A practical flow synthesis of 1,2,3-triazoles. RSC Adv
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| Additional Infomation |
This compound is a research tool for PROTAC development and targeted protein degradation studies. It is not an approved therapeutic. The terminal azide group allows conjugation with alkyne-functionalized target-binding ligands via copper-catalyzed or copper-free click chemistry for rapid PROTAC library generation.
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| Molecular Formula |
C29H40N6O8
|
|---|---|
| Molecular Weight |
600.66
|
| Exact Mass |
600.29
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| CAS # |
2300178-66-7
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| PubChem CID |
163335681
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
1.01
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
21
|
| Heavy Atom Count |
43
|
| Complexity |
1000
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)CCCCCOCCOCCOCCCCCCN=[N+]=[N-]
|
| InChi Key |
JUXLQOHNAZVQSN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H40N6O8/c30-34-31-14-5-1-2-6-15-41-17-19-43-20-18-42-16-7-3-4-11-24(36)32-22-10-8-9-21-26(22)29(40)35(28(21)39)23-12-13-25(37)33-27(23)38/h8-10,23H,1-7,11-20H2,(H,32,36)(H,33,37,38)
|
| Chemical Name |
6-[2-[2-(6-azidohexoxy)ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]hexanamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| 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 | 1.6648 mL | 8.3242 mL | 16.6484 mL | |
| 5 mM | 0.3330 mL | 1.6648 mL | 3.3297 mL | |
| 10 mM | 0.1665 mL | 0.8324 mL | 1.6648 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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