| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
The primary target is the E3 ubiquitin ligase complex protein Cereblon (CRBN). The pomalidomide moiety binds to CRBN, which is a substrate receptor of the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex. This complex is responsible for recruiting target proteins for ubiquitination and subsequent proteasomal degradation. The linker and terminal chlorine facilitate conjugation to a target protein ligand.
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| ln Vitro |
In vitro, this E3 ligase ligand-linker conjugate serves as a building block for synthesizing PROTACs. The final PROTAC molecule induces ubiquitination and degradation of the target protein of interest via the ubiquitin-proteasome pathway. The pomalidomide moiety retains CRBN-binding affinity, which is essential for its function. Detailed quantitative data (e.g., Kd for CRBN) for this specific linker conjugate is not provided; however, the parent compound pomalidomide binds CRBN with high affinity.
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| ln Vivo |
As a building block for PROTACs, this compound is not a fully active agent itself; it must be conjugated to a target protein binder to be functional. In vivo efficacy studies would be conducted with the complete PROTAC molecule. The linker and chlorine handle are designed to provide the spatial flexibility and conjugation site necessary for the final PROTAC to effectively engage both the target protein and CRBN simultaneously, leading to ubiquitination and proteasomal degradation in cells.
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| Enzyme Assay |
The standard non-cellular assay for CRBN binding is a fluorescence polarization (FP) competition binding assay. Recombinant CRBN-DDB1 complex is incubated with a fluorescently labeled pomalidomide probe (or a known CRBN-binding tracer). The test compound (Pomalidomide-amido-C5-PEG2-C6-chlorine) is serially diluted and added to the mixture. The degree of polarization is measured, and the inhibition constant (Ki) or half-maximal inhibitory concentration (IC50) is calculated by comparing the displacement of the tracer.
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| Cell Assay |
This conjugate is typically used in cell-based assays only after conjugation to a target protein ligand to form a complete PROTAC. To assess the functional activity of the resulting PROTAC, cells expressing the target protein are treated with the PROTAC at varying concentrations for 4-24 hours. Target protein degradation is measured by Western blot. A cereblon-dependent degradation mechanism is confirmed by pre-treating cells with a proteasome inhibitor (e.g., MG132) or by using a CRBN knockout cell line. Proliferation assays (e.g., MTT, CellTiter-Glo) are used to assess phenotypic consequences.
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| Animal Protocol |
In vivo studies are performed with the final PROTAC molecule rather than the linker conjugate alone. In a typical PROTAC in vivo efficacy study, a mouse xenograft model of a cancer that is dependent on the target protein is used. Mice are treated with the PROTAC (e.g., via intraperitoneal or oral administration). Tumor volume and body weight are monitored. At the end of the study, tumor and tissue lysates are analyzed for target protein levels by Western blot and for engagement of the ubiquitin-proteasome system. The inclusion of the PEG-based linker is intended to enhance solubility, cellular permeability, and precise protein-ligase engagement.
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| ADME/Pharmacokinetics |
Pomalidomide-amido-C5-PEG2-C6-chlorine is a synthetic building block with a molecular weight of 594.1 and a molecular formula of C29H40ClN3O8. It is soluble in DMSO (100 mg/mL). The linker is PEG-based (C5-PEG2-C6), which is designed to increase water solubility and flexibility compared to purely alkyl linkers. For storage, it is recommended to keep as a powder at 4degC under nitrogen and as a solution at -80degC for up to 6 months or -20degC for up to 1 month.
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| Toxicity/Toxicokinetics |
As a research building block that is not the final active agent, toxicity data is not directly reported. The pomalidomide component is based on the immunomodulatory drug (IMiD) pomalidomide, which has a known clinical safety profile but is associated with teratogenicity, thrombosis, and myelosuppression. Therefore, handling with appropriate precautions is recommended. The reactive chlorine handle suggests it should be handled as a potential alkylating agent, and standard safety precautions for organic synthetic intermediates should be used.
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| References |
[1]. Lai AC, et al. Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL. Angew Chem Int Ed Engl. 2016 Jan 11;55(2):807-10.
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| Additional Infomation |
Pomalidomide-amido-C5-PEG2-C6-chlorine is a derivative of pomalidomide, a third-generation IMiD drug approved for the treatment of multiple myeloma. This compound is not a drug itself but a research tool for PROTAC (proteolysis-targeting chimera) technology development. PROTACs are heterobifunctional molecules that induce targeted protein degradation, representing a new therapeutic modality. The use of PEG-based linkers often improves pharmacokinetic properties. This product is exclusively for research purposes, particularly in targeted protein degradation and drug discovery, and is not intended for therapeutic use.
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| Exact Mass |
593.25
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|---|---|
| CAS # |
1835705-69-5
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| PubChem CID |
129072761
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
41
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| Complexity |
888
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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)CCCCCOCCOCCOCCCCCCCl
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| InChi Key |
CEGOWZXGBJKMOC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H40ClN3O8/c30-14-5-1-2-6-15-39-17-19-41-20-18-40-16-7-3-4-11-24(34)31-22-10-8-9-21-26(22)29(38)33(28(21)37)23-12-13-25(35)32-27(23)36/h8-10,23H,1-7,11-20H2,(H,31,34)(H,32,35,36)
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| Chemical Name |
6-[2-[2-(6-chlorohexoxy)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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (168.32 mM )
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.22 mg/mL (3.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 22.2 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
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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