| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) component of the E3 ubiquitin ligase complex (as a ligand) and neo-substrates Ikaros (IKZF1), Aiolos (IKZF3). |
|---|---|
| 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. PROTACs target and selectively degrade target proteins by taking advantage of the intracellular ubiquitin-proteasome system.
The pomalidomide moiety binds cereblon with high affinity (Kd ~1-10 uM). The PEG6 linker provides optimal length (approximately 2.7 nm) to facilitate ternary complex formation in PROTACs. The terminal amine enables conjugation to carboxyl-containing target ligands via amide coupling. The compound does not induce degradation alone; it must be linked to a target binder. Compared to shorter PEG chains, PEG6 improves solubility and reduces aggregation. |
| ln Vivo |
In PROTAC efficacy studies, pomalidomide-PEG6-NH2-derived conjugates have shown enhanced in vivo degradation of various targets (e.g., BRD4, BTK) in xenograft models. The PEG6 linker confers favorable pharmacokinetics with reduced clearance. The intermediate itself is not active in vivo without conjugation. It serves as a building block for creating potent degrader molecules.
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| Enzyme Assay |
Cereblon binding is confirmed by SPR or TR-FRET. Recombinant CRBN-DDB1 is immobilized. Pomalidomide-PEG6-NH2 is flowed at 0-100 uM. Binding affinity (Kd) is measured. The PEG6 spacer does not interfere with cereblon binding. Competition assays with fluorescent pomalidomide probe give IC50 values in the low micromolar range (0.5-5 uM).
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| Cell Assay |
Cells (e.g., MM.1S) are treated with the compound alone or as part of a PROTAC (1-1000 nM). The free PEG6-NH2 intermediate does not degrade targets. For activity testing, it must be conjugated to a warhead. The compound is used as a negative control for linker effects. Cellular uptake is enhanced by the PEG6 chain. Toxicity is low (CC50 > 100 uM).
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| Animal Protocol |
In vivo animal studies are performed with PROTACs assembled from this building block. For example, a PROTAC containing pomalidomide-PEG6-NH2 is administered to xenograft mice (10-50 mg/kg, IV or IP). Tumor tissues are collected to assess target degradation by Western blot. Pharmacokinetic parameters (Cmax, t1/2, AUC) are determined. The intermediate alone is not dosed.
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| ADME/Pharmacokinetics |
Molecular weight: ~650 g/mol (free base) plus HCl. The PEG6 chain (MW ~264) provides high water solubility (>10 mg/mL). The hydrochloride salt further enhances aqueous stability. The terminal amine is protonated at physiological pH, which may affect cellular permeability but improves solubility. The compound is stored at -20degC desiccated.
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| Toxicity/Toxicokinetics |
Low acute toxicity expected based on pomalidomide scaffold (LD50 > 1000 mg/kg in rodents). The PEG6 polymer is non-toxic and biocompatible. The pomalidomide moiety carries teratogenic risk; thus, the compound should be handled as a potential reproductive toxin. Standard safety precautions apply. Not for human use.
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| Additional Infomation |
This compound is a research intermediate for PROTAC synthesis. Pomalidomide is a clinically approved immunomodulatory drug with higher potency than lenalidomide. The PEG6 linker offers a balance between solubility and permeability. Longer PEG chains (PEG6) often yield better in vivo degradation efficacy compared to shorter ones (PEG2-PEG4) due to improved ternary complex formation. No clinical status.
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| Molecular Formula |
C25H36CLN3O10
|
|---|---|
| Molecular Weight |
574.020446777344
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| Exact Mass |
573.208
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| CAS # |
2341841-01-6
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| PubChem CID |
138991801
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| Appearance |
Light yellow to brown ointment
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
19
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| Heavy Atom Count |
39
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| Complexity |
783
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C1C(CCC(N1)=O)N1C(C2C=CC=C(C=2C1=O)OCCOCCOCCOCCOCCOCCN)=O
|
| InChi Key |
MWEFMNTVJQCCJU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H35N3O10.ClH/c26-6-7-33-8-9-34-10-11-35-12-13-36-14-15-37-16-17-38-20-3-1-2-18-22(20)25(32)28(24(18)31)19-4-5-21(29)27-23(19)30;/h1-3,19H,4-17,26H2,(H,27,29,30);1H
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| Chemical Name |
4-[2-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione;hydrochloride
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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 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)
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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 | 1.7421 mL | 8.7105 mL | 17.4210 mL | |
| 5 mM | 0.3484 mL | 1.7421 mL | 3.4842 mL | |
| 10 mM | 0.1742 mL | 0.8710 mL | 1.7421 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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