| Size | Price | Stock | Qty |
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| 1g |
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| Other Sizes |
| Targets |
m-PEG12-OH functions as a PEG-based linker in PROTACs and ADCs, connecting a target-binding ligand to an E3 ubiquitin ligase ligand or a cytotoxic payload. The 12-unit PEG chain provides an optimal length and flexibility to facilitate the formation of a stable ternary complex between the target protein, the PROTAC, and the E3 ligase. As a non-cleavable ADC linker, it provides a stable connection between the antibody and the payload, ensuring that the drug is not released prematurely in circulation. The hydrophilic PEG spacer also helps to mask hydrophobic regions of the molecule, reducing aggregation and improving overall pharmacokinetic properties.
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| ln Vitro |
Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. PROTAC selectively degrades target proteins by means of the intracellular ubiquitin-proteasome system [1]. ADC is made up of antibodies that are connected to ADC cytotoxins by an ADC linker [2].
In vitro, m-PEG12-OH is used in the synthesis of PROTACs that demonstrate potent degradation of target proteins. The PEG linker's flexibility and optimal length (12 units) have been shown to enhance the degradation efficiency (DC50) and maximum degradation (Dmax) in cell-based assays. Studies have indicated that PROTACs with PEG linkers of this length exhibit improved cellular uptake and target engagement compared to those with shorter or longer linkers. As a non-cleavable ADC linker, it ensures that the cytotoxic payload remains attached to the antibody until the ADC is internalized and degraded in the lysosome, providing a stable and effective drug delivery system. |
| ln Vivo |
In vivo, m-PEG12-OH-based PROTACs and ADCs have demonstrated favorable pharmacokinetic profiles. The hydrophilic PEG chain increases the hydrodynamic volume of the conjugate, reducing renal clearance and prolonging the half-life in circulation. The PEG spacer also minimizes opsonization and recognition by the reticuloendothelial system, leading to improved systemic exposure. In animal models, PROTACs containing this PEG linker have shown effective target protein degradation in various tissues, while ADCs have demonstrated potent antitumor efficacy with reduced off-target toxicity. The non-cleavable nature of the linker ensures stable drug delivery to the target site.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for m-PEG12-OH-based molecules are performed to evaluate the binding affinity of the complete conjugate to its target. Surface plasmon resonance (SPR) or biolayer interferometry (BLI) is used to measure the binding kinetics (ka, kd, and KD) of the PROTAC or ADC to its target protein and the E3 ligase. The role of the PEG linker is assessed by comparing the binding affinities of conjugates with different linker lengths and compositions. Competitive binding assays using fluorescently labeled probes can also be employed to determine the IC50 values. Additionally, the solubility enhancement provided by the PEG linker is evaluated using standard solubility assays in aqueous buffers.
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| Cell Assay |
In vitro cellular experiments for m-PEG12-OH-based PROTACs are performed to evaluate target protein degradation. Cells are treated with varying concentrations of the PROTAC for 4-24 hours, and the levels of the target protein are quantified by Western blot or high-content imaging. The DC50 and Dmax values are calculated from dose-response curves. To confirm that degradation is mediated by the ubiquitin-proteasome system, cells are co-treated with a proteasome inhibitor such as MG132, which should block the degradation. Cellular uptake and intracellular distribution of the PROTAC can be assessed using fluorescently labeled analogues.
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| Animal Protocol |
In vivo animal studies for m-PEG12-OH-based PROTACs are conducted using xenograft or transgenic mouse models. The PROTAC is administered via intravenous, intraperitoneal, or oral routes at various doses. Target protein degradation in tissues such as tumor, liver, and kidney is assessed by Western blot or immunohistochemistry at different time points post-administration. Pharmacodynamic markers downstream of the target protein are also measured to confirm the functional consequences of degradation. The antitumor efficacy of the PROTAC is evaluated by monitoring tumor growth inhibition and overall survival.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of m-PEG12-OH-based molecules are significantly improved by the PEG chain. The hydrophilic PEG spacer increases the hydrodynamic volume, reducing renal clearance and prolonging the half-life in circulation. The PEG chain also minimizes opsonization and recognition by the reticuloendothelial system, further enhancing systemic exposure. Typically, these conjugates exhibit a prolonged half-life and a larger volume of distribution compared to non-PEGylated analogues. The area under the curve (AUC) is significantly higher, indicating improved bioavailability.
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| Toxicity/Toxicokinetics |
The toxicity profile of m-PEG12-OH-based molecules is generally favorable due to the biocompatibility of PEG. However, high doses of PEGylated compounds can sometimes lead to vacuolation in tissues such as the renal proximal tubules and the choroid plexus. In preclinical studies, toxicity is assessed by monitoring body weight, clinical signs, and histopathological changes in major organs. Hematological and serum biochemical parameters are also evaluated to detect any organ-specific toxicity. The overall safety profile of PEG-based conjugates is considered acceptable for research applications.
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| References | |
| Additional Infomation |
m-PEG12-OH is a versatile PEG-based linker used in both PROTAC and ADC synthesis. Its 12-unit PEG chain provides optimal length and flexibility for efficient ternary complex formation in PROTACs and stable conjugation in ADCs. The compound's methoxy termination and hydroxyl group allow for easy functionalization. As a research tool, m-PEG12-OH is essential for developing targeted protein degraders and antibody-drug conjugates with improved solubility, stability, and pharmacokinetic properties. Its monodisperse nature ensures reproducibility in research applications.
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| Molecular Formula |
C25H52O13
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| Molecular Weight |
560.672590255737
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| Exact Mass |
560.34
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| CAS # |
2050595-03-2
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| PubChem CID |
14550548
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| Appearance |
Colorless to light yellow liquid
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| LogP |
-2.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
35
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| Heavy Atom Count |
38
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| Complexity |
408
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO
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| InChi Key |
PLQZJIIDLZRWBG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H52O13/c1-27-4-5-29-8-9-31-12-13-33-16-17-35-20-21-37-24-25-38-23-22-36-19-18-34-15-14-32-11-10-30-7-6-28-3-2-26/h26H,2-25H2,1H3
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| Chemical Name |
2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol
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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 | 1.7836 mL | 8.9179 mL | 17.8358 mL | |
| 5 mM | 0.3567 mL | 1.7836 mL | 3.5672 mL | |
| 10 mM | 0.1784 mL | 0.8918 mL | 1.7836 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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