| Size | Price | |
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| Other Sizes |
| Targets |
PEGs
Benzyl-PEG8-alcohol does not have a biological target. As a PEG‑based linker, it is chemically inert and does not bind to any receptor, enzyme, or nucleic acid. Its role is to serve as a spacer in heterobifunctional molecules (e.g., PROTACs) to connect a warhead (targeting a protein of interest) to a ligand for an E3 ubiquitin ligase. The PEG chain improves aqueous solubility, reduces aggregation, and enhances the pharmacokinetic properties of the conjugate. The benzyl group can be removed by hydrogenolysis to reveal a phenol or further functionalized. Thus, there is no in vitro or in vivo activity attributed to the linker itself. |
|---|---|
| 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. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
Benzyl-PEG8-alcohol has no direct in vitro biological activity because it lacks a protein‑binding moiety. In cell‑based assays, the linker alone does not induce cytotoxicity, modulate signaling pathways, or affect cell viability at concentrations up to 100 uM. However, when incorporated into a PROTAC, the linker contributes to the overall degradation efficiency and selectivity by optimizing the distance and orientation between the warhead and the E3 ligase ligand. In control experiments, the free linker is used to confirm that any observed biological effect (e.g., target degradation) is due to the conjugate and not the linker. No EC50 or IC50 values are applicable for the linker alone. |
| ln Vivo |
Benzyl-PEG8-alcohol is not administered as a standalone compound in animal studies, because it has no therapeutic effect. In pharmacokinetic studies of PEG‑based linkers, they are rapidly cleared and have very low systemic exposure due to their hydrophilicity. When used as part of a PROTAC, the linker influences the conjugate's in vivo stability, distribution, and clearance. For example, longer PEG chains reduce liver microsomal metabolism and increase plasma half‑life of the conjugate. However, the free linker itself is considered a non‑toxic, metabolically inert excipient. No in vivo efficacy data exist for Benzyl-PEG8-alcohol alone.
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| Enzyme Assay |
The physicochemical properties of Benzyl-PEG8-alcohol are characterized using standard analytical techniques, but there is no enzyme/receptor binding assay for this linker. Instead, the purity and identity are confirmed by HPLC, NMR, and mass spectrometry. A typical quality control protocol involves reverse‑phase HPLC on a C18 column with a mobile phase of water/acetonitrile (0.1% TFA), detecting at 210 nm or using evaporative light scattering detection (ELSD). The compound should show a single peak with purity ≥95%. NMR (¹H and ¹3C) in CDCl3 or DMSO‑d₆ confirms the presence of the benzyl group (delta 7.2‑7.4 ppm) and the PEG backbone (delta 3.5‑3.7 ppm). No biological binding assays are performed.
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| Cell Assay |
No cell‑based assays are performed with Benzyl-PEG8-alcohol alone because it lacks biological activity. However, in the context of validating a synthetic linker for PROTAC construction, researchers may treat cells with the free linker as a negative control. For example, cells (e.g., HEK293T or HeLa) are seeded in 6‑well plates at 5×10⁵ cells/well and incubated with the linker at 10‑100 uM for 24‑48 hours. Cell viability is measured by MTT or trypan blue exclusion; no significant reduction in viability should occur compared to vehicle control (0.1% DMSO). This confirms that the linker does not cause off‑target toxicity. No other cellular responses (e.g., protein degradation, signaling activation) are expected.
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| Animal Protocol |
In vivo experiments using Benzyl-PEG8-alcohol alone are not typical. If necessary for a toxicology assessment, the compound may be administered to rodents (e.g., CD‑1 mice) as a single intravenous or oral dose. Formulate in saline or PBS (since the linker is water‑soluble) at concentrations up to 50 mg/mL. Administer at 10‑100 mg/kg and observe animals for 14 days for signs of toxicity, including body weight change, behavioral changes, and mortality. Blood samples are collected for PK analysis. However, such studies are rarely performed because the linker is considered inert. Most often, the linker is evaluated as part of a conjugate in xenograft models (e.g., subcutaneous tumor‑bearing mice), where the conjugate is dosed at 1‑30 mg/kg.
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| ADME/Pharmacokinetics |
Benzyl-PEG8-alcohol (CAS 477775-73-8) has the molecular formula C23H40O₉ and molecular weight 460.56 g/mol. It is a colorless to pale yellow oil or viscous liquid at room temperature, with >95% purity. The compound is highly soluble in water, DMSO, ethanol, and dichloromethane. Its logP (calculated) is approximately 0.3, indicating high hydrophilicity. The terminal alcohol can be further derivatized (e.g., tosylation, mesylation, or conversion to an amine) for conjugation. The benzyl group can be removed by hydrogenation (H2, Pd/C) to give the corresponding phenol, which is useful for attaching to carboxylic acids via ester bonds. Store at 2‑8degC under inert atmosphere (N2 or Ar) to prevent oxidation. Shelf life is at least 2 years when stored properly.
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| Toxicity/Toxicokinetics |
Benzyl-PEG8-alcohol is considered non‑toxic under normal laboratory handling conditions. The Safety Data Sheet (SDS) typically classifies it as a non‑hazardous substance. Acute oral toxicity (LD50) is expected to be >2000 mg/kg in rats (based on similar PEG compounds). It is not a skin irritant, eye irritant, or skin sensitizer. No mutagenicity (Ames test) or reproductive toxicity data are available, but due to its inert nature and lack of reactive groups (except the alcohol), it is unlikely to be genotoxic. However, as with any chemical, avoid ingestion, inhalation, and prolonged skin contact. Use standard personal protective equipment (gloves, lab coat, safety glasses). In case of accidental ingestion, seek medical advice. There is no specific antidote; treatment is symptomatic.
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| References |
[1]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562
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| Additional Infomation |
Benzyl-PEG8-alcohol is a commonly used linker in PROTAC synthesis, especially for creating degraders with improved solubility and reduced aggregation. The PEG8 chain length provides an optimal distance (approximately 3‑4 nm) for bridging a target protein and an E3 ligase. The compound is also used to prepare PEGylated dyes, affinity probes, and polymer conjugates. It is not approved for any clinical or therapeutic indication. The synthesis involves reacting benzyl alcohol with ethylene glycol oligomers under basic conditions. The CAS number 477775-73-8 is specific for the PEG8 variant; shorter or longer PEG homologs have different CAS numbers. For research use only, not for diagnostic or veterinary use. Store away from strong oxidizers. Always check the purity certificate before use in sensitive biological conjugations.
|
| Molecular Formula |
C23H40O9
|
|---|---|
| Molecular Weight |
460.56
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| Exact Mass |
460.267
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| CAS # |
477775-73-8
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| PubChem CID |
57437703
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| Appearance |
Colorless to light yellow liquid（Density：1.101±0.06 g/cm3）
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| LogP |
1.311
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
25
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| Heavy Atom Count |
32
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| Complexity |
354
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC=C(C=C1)COCCOCCOCCOCCOCCOCCOCCOCCO
|
| InChi Key |
KFJXPXAFUAPRSZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H40O9/c24-6-7-25-8-9-26-10-11-27-12-13-28-14-15-29-16-17-30-18-19-31-20-21-32-22-23-4-2-1-3-5-23/h1-5,24H,6-22H2
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| Chemical Name |
2-[2-[2-[2-[2-[2-[2-(2-phenylmethoxyethoxy)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 | 2.1713 mL | 10.8563 mL | 21.7127 mL | |
| 5 mM | 0.4343 mL | 2.1713 mL | 4.3425 mL | |
| 10 mM | 0.2171 mL | 1.0856 mL | 2.1713 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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