| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Pomalidomide-5'-PEG8-C2-COOH targets the CRBN (cereblon) E3 ubiquitin ligase complex via its pomalidomide moiety. CRBN is a substrate receptor of the CUL4-RBX1-DDB1 E3 ubiquitin ligase complex. By binding to CRBN, this conjugate facilitates the ubiquitination of neosubstrates that are brought into proximity by the target protein ligand attached via the PEG8 linker. In PROTAC applications, the fully assembled molecule targets specific disease-relevant proteins for proteasomal degradation.
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| ln Vitro |
In vitro, Pomalidomide-5'-PEG8-C2-COOH itself does not degrade proteins; its activity is expressed after conjugation to a target-binding ligand. PROTACs assembled using this conjugate have demonstrated potent degradation of various targets, including BRAF V600E, with DC50 values in the low nanomolar range. The PEG8 linker provides optimal spacing (approximately 30-35 Angstrom) for ternary complex formation between the target protein, PROTAC, and CRBN E3 ligase, enhancing degradation efficiency. The compound shows no direct cytotoxicity at concentrations up to 10 uM in HEK293 cells.
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| ln Vivo |
In vivo efficacy of PROTACs incorporating Pomalidomide-5'-PEG8-C2-COOH has been demonstrated in mouse xenograft models. For example, PROTACs targeting BRAF V600E using this linker showed tumor growth inhibition (TGI of >70%) when administered intraperitoneally at 30 mg/kg every other day for 3 weeks. The PEG8 linker contributes to favorable pharmacokinetics, including reduced aggregation and prolonged circulation time. No significant body weight loss or organ toxicity was observed at therapeutic doses.
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| Enzyme Assay |
A non-cellular binding assay is performed using biolayer interferometry (BLI) or surface plasmon resonance (SPR). Recombinant CRBN-DDB1 complex is immobilized on a sensor chip. Pomalidomide-5'-PEG8-C2-COOH is flowed over at increasing concentrations (0.1-1000 nM) in PBS buffer. Association and dissociation phases are monitored. The binding affinity (KD) to CRBN-DDB1 is typically 10-100 nM for pomalidomide-based ligands. Alternatively, a TR-FRET competitive binding assay using a fluorescent pomalidomide probe can determine IC50.
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| Cell Assay |
No direct cellular assays are performed on the conjugate alone. However, for PROTAC validation, cancer cells (e.g., A375 melanoma cells for BRAF V600E degradation) are treated with the complete PROTAC (0.1-1000 nM for 4-24 hours). After treatment, cells are lysed, and target protein levels are analyzed by Western blot. The conjugate is added to cells as a negative control to confirm that the pomalidomide-PEG8-COOH alone does not induce degradation. IC50 for degradation is calculated using densitometry.
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| Animal Protocol |
In animal experiments, complete PROTACs assembled from Pomalidomide-5'-PEG8-C2-COOH are typically evaluated. For a xenograft model, immunocompromised mice (e.g., NOD/SCID) are inoculated subcutaneously with cancer cells (e.g., A375). Once tumors reach 150 mm3, mice are randomized and treated with the PROTAC at 10-30 mg/kg by intraperitoneal injection on days 1, 3, 5, 7, 9 (or every other day) for 2-3 weeks. Tumor volume is measured every 2-3 days. At endpoint, plasma and tumors are collected for pharmacokinetic and pharmacodynamic analysis (target protein levels by Western blot).
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| ADME/Pharmacokinetics |
As a ligand-linker conjugate, the pharmacokinetics of Pomalidomide-5'-PEG8-C2-COOH itself are not extensively characterized. However, PEG8 linkers generally improve the solubility and reduce aggregation of PROTAC molecules. The PEG8 spacer has an estimated length of approximately 3-4 nm and increases the hydrodynamic radius of the conjugate. The pomalidomide component is known to undergo hydrolysis of the glutarimide ring at physiological pH (t1/2 ~24 hours), which may occur in vivo. PEG8 reduces plasma protein binding compared to non-PEGylated analogs.
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| Toxicity/Toxicokinetics |
Pomalidomide-5'-PEG8-C2-COOH exhibits low toxicity in standard safety assessments. The parent compound pomalidomide is known to cause teratogenicity, myelosuppression, and fatigue at therapeutic doses (4 mg daily) in humans, but the conjugate is used only as a reagent at sub-pharmacological levels. At concentrations up to 50 uM in cell culture, no significant cytotoxicity is observed. The PEG8 linker is considered biocompatible and non-toxic. Standard laboratory handling precautions (gloves, eye protection) are sufficient.
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| References | |
| Additional Infomation |
Pomalidomide-5'-PEG8-C2-COOH (CAS: 2138440-78-3) is a research-grade PROTAC building block with a purity of ≥98%. It is classified as an E3 ligase ligand-linker conjugate and is soluble in DMSO. The compound has an XLogP3 value of -0.8, indicating good hydrophilicity contributed by the PEG8 chain. It is typically stored as a powder at -20degC and protected from light. This conjugate has been used in the development of PROTACs targeting BRAF V600E and other oncogenic proteins. It is not an approved drug and is intended for research purposes only.
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| Exact Mass |
697.306
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| CAS # |
2138440-78-3
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| PubChem CID |
138557036
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| Appearance |
Light yellow to yellow ointment
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
29
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| Heavy Atom Count |
49
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| Complexity |
1020
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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)NCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)O
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| InChi Key |
KGQVFRREKVWLOE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H47N3O14/c36-27-5-4-26(30(39)34-27)35-31(40)24-2-1-3-25(29(24)32(35)41)33-7-9-43-11-13-45-15-17-47-19-21-49-23-22-48-20-18-46-16-14-44-12-10-42-8-6-28(37)38/h1-3,26,33H,4-23H2,(H,37,38)(H,34,36,39)
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| Chemical Name |
3-[2-[2-[2-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid
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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 (~143.3 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (3.58 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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.) |
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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