| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| Other Sizes |
| Targets |
Cereblon
The primary molecular target of Pomalidomide-amido-PEG3-C2-NH2 is cereblon (CRBN), an E3 ubiquitin ligase substrate receptor. As a ligand for the E3 ubiquitin ligase complex, this compound binds to CRBN and recruits the ubiquitin-proteasome system. In the context of PROTAC technology, the pomalidomide moiety serves as the E3 ligase recognition element, while the PEG3-C2 linker provides a spacer for conjugation to a target protein ligand. This bifunctional design enables the targeted degradation of specific proteins by bringing the target protein into proximity with the E3 ligase. |
|---|---|
| ln Vitro |
BI-3663 can be synthesized using pomalidomide-amido-PEG3-C2-NH2 (Compound 5b). Focal adhesion tyrosine kinase (PTK2) is degraded by BI-3663 (cereblon-based) in a panel of 11 human hepatocellular carcinoma (HCC) cell lines from a median DC50 of 30 nM to >80%[1].
In vitro studies demonstrate that Pomalidomide-amido-PEG3-C2-NH2 functions as a key component in PROTAC molecules. The compound can be used to synthesize BI-3663, a cereblon-based PROTAC that degrades focal adhesion tyrosine kinase (PTK2) with a median DC50 of 30 nM to >80% across a panel of 11 human hepatocellular carcinoma (HCC) cell lines. The PEG3 spacer provides appropriate length and flexibility for the formation of the ternary complex between the target protein, PROTAC, and E3 ligase. This compound is designed to facilitate targeted protein degradation in cellular systems through the ubiquitin-proteasome pathway. |
| ln Vivo |
In vivo activity data for Pomalidomide-amido-PEG3-C2-NH2 as a standalone compound are not reported, as it is utilized as a synthetic intermediate or linker component in PROTAC design rather than as a therapeutic agent itself. The in vivo efficacy of PROTAC molecules incorporating this pomalidomide-based ligand and PEG3-C2 linker, such as BI-3663, would depend on the specific target protein ligand and the overall pharmacokinetic properties of the complete PROTAC construct. As a linker conjugate, its primary role is to facilitate targeted protein degradation through E3 ligase recruitment.
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| Enzyme Assay |
In vitro assays for evaluating Pomalidomide-amido-PEG3-C2-NH2 typically involve binding studies to assess its interaction with cereblon (CRBN), the E3 ubiquitin ligase substrate receptor. Surface plasmon resonance (SPR) or fluorescence polarization techniques can be used to measure the binding affinity (Kd) between the pomalidomide-based ligand and CRBN. Additionally, ternary complex formation assays can be performed to evaluate the ability of PROTAC molecules containing this linker to simultaneously engage both the E3 ligase and the target protein. Competition binding assays using fluorescently labeled probes are also commonly used to determine the inhibitory concentration (IC50) of the ligand for CRBN binding.
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| Cell Assay |
In vitro cell-based assays for Pomalidomide-amido-PEG3-C2-NH2 typically involve its incorporation into PROTAC molecules followed by evaluation of target protein degradation in cultured cells. Cells are treated with PROTACs containing this pomalidomide-based ligand and PEG3-C2 linker, and the levels of the target protein are measured by Western blotting or immunofluorescence to assess degradation efficiency. Dose-response experiments are performed to determine the DC50 (half-maximal degradation concentration) of the PROTAC construct. Additionally, cell viability and proliferation assays may be conducted to evaluate the functional consequences of target protein degradation.
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| Animal Protocol |
In vivo animal studies using Pomalidomide-amido-PEG3-C2-NH2 are conducted as part of the evaluation of complete PROTAC molecules that incorporate this pomalidomide-based ligand and PEG3-C2 linker. Typical protocols involve administering PROTAC constructs such as BI-3663 to mouse xenograft models or disease-relevant animal models, followed by assessment of target protein degradation in harvested tissues via Western blot or immunohistochemistry. Pharmacodynamic endpoints include measurement of target protein levels, downstream signaling pathway modulation, and tumor growth inhibition in efficacy studies. Dosing regimens are optimized based on the pharmacokinetic properties of the specific PROTAC construct.
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| ADME/Pharmacokinetics |
As a linker conjugate rather than a therapeutic drug, comprehensive pharmacokinetic data for Pomalidomide-amido-PEG3-C2-NH2 alone are limited. The compound has a molecular formula of C22H28N4O8 and a molecular weight of 476.48. The IUPAC name is 3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)-N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)propanamide. When incorporated into PROTAC molecules, the pomalidomide-based ligand and PEG3-C2 linker contribute to the overall physicochemical properties of the complete construct.
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| Toxicity/Toxicokinetics |
The toxicity profile of Pomalidomide-amido-PEG3-C2-NH2 as an individual compound is not extensively characterized, as it is primarily used as a research reagent and synthetic intermediate for PROTAC development. The compound is intended for research use only and is not approved for therapeutic use in humans. Pomalidomide is known to have immunomodulatory effects and teratogenic potential, and appropriate safety precautions should be taken when handling this compound. Standard laboratory safety practices, including the use of personal protective equipment and handling in a fume hood, are recommended.
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| References | |
| Additional Infomation |
Pomalidomide-amido-PEG3-C2-NH2 (CAS 2328070-52-4) has a molecular formula of C22H28N4O8 and a molecular weight of 476.48. The compound has a purity of ≥98%. It is also known as Cereblon Ligand-Linker Conjugates 22 and E3 ligase Ligand-Linker Conjugates 55. The compound can be used to synthesize BI-3663, which degrades PTK2 with a median DC50 of 30 nM. It is part of the PROTAC linker category and is used in E3 ligase ligand-linker conjugate applications.
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| Molecular Formula |
C22H28N4O8
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|---|---|
| Molecular Weight |
476.479725837708
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| Exact Mass |
476.19
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| CAS # |
2328070-52-4
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| PubChem CID |
145712393
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
-1.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
34
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| Complexity |
776
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)CCOCCOCCOCCN
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| InChi Key |
FEXCPYUYLOFYGF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H28N4O8/c23-7-9-33-11-13-34-12-10-32-8-6-18(28)24-15-3-1-2-14-19(15)22(31)26(21(14)30)16-4-5-17(27)25-20(16)29/h1-3,16H,4-13,23H2,(H,24,28)(H,25,27,29)
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| Chemical Name |
3-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]propanamide
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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) |
DMSO :~100 mg/mL (~209.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.25 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 25.0 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: ≥ 2.5 mg/mL (5.25 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0987 mL | 10.4936 mL | 20.9872 mL | |
| 5 mM | 0.4197 mL | 2.0987 mL | 4.1974 mL | |
| 10 mM | 0.2099 mL | 1.0494 mL | 2.0987 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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