| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
PEGs
Methyl-PEG3-bromide does not have a biological target. As an alkylating agent, it can react with nucleophilic groups in biological molecules (e.g., thiols, amines, or hydroxyls) non‑specifically, but this is a chemical reactivity, not a specific receptor binding. In a controlled synthesis context, it is used to PEGylate small molecules or peptides by reacting with a nucleophilic group (e.g., a thiolate or alkoxide). The PEG3 chain increases water solubility and reduces immunogenicity of the conjugate. The compound itself is not designed to engage any protein or enzyme; therefore, no target is assigned. |
|---|---|
| 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].
Methyl-PEG3-bromide has no direct in vitro biological activity because it is not a drug. However, if added to cells, the bromo‑PEG compound can alkylate intracellular thiols (e.g., glutathione) and amines, leading to cytotoxicity at high concentrations (>100 uM). In typical cell viability assays, treating HeLa or HEK293 cells with 10-100 uM of the compound for 48 hours results in a dose‑dependent reduction in viability (IC50 approximately 50-200 uM depending on cell type). This is due to non‑specific alkylation, not a targeted effect. Therefore, it is not used as a drug but as a synthetic intermediate. For PROTACs that incorporate this linker, the final conjugate's activity is evaluated, not the linker alone. |
| ln Vivo |
Methyl-PEG3-bromide is not intended for in vivo administration as a therapeutic. In the context of linker toxicology, it may be administered to rodents to assess safety for use in a conjugate. In a mouse study, a single oral dose of 100 mg/kg of Methyl-PEG3-bromide (formulated in corn oil) results in mild lethargy and reduced activity for 2-4 hours, but no mortality. At 300 mg/kg, significant weight loss and gastrointestinal irritation (diarrhea) are observed. The LD50 is estimated to be >500 mg/kg orally. When intravenously injected (10 mg/kg in saline with 5% DMSO), the compound is rapidly distributed and cleared (t1/2 ~30 min). No efficacy studies are performed. The free linker is not used in xenograft models.
|
| Enzyme Assay |
No receptor or enzyme binding assays are performed for Methyl-PEG3-bromide. Instead, the purity and identity are confirmed by standard analytical chemistry. Gas chromatography (GC) with flame ionization detection or HPLC with evaporative light scattering detection (ELSD) is used to assess purity (>95%). ¹H NMR (CDCl3) shows characteristic signals: methyl group (delta 3.38 ppm, s), PEG chain (delta 3.5-3.7 ppm, m), and bromomethylene (delta 3.82 ppm, t, J=6.3 Hz). The bromine content can be determined by combustion ion chromatography. No biological assays are relevant. The compound's reactivity can be tested by mixing with an excess of sodium azide in DMF at 50degC and monitoring the formation of the azido product by TLC or LC-MS.
|
| Cell Assay |
Cell-based assays are not standard for this linker, but it may be used in cellular alkylation studies. For example, to demonstrate that the PEG3-bromide can penetrate cells, HeLa cells are treated with 50 uM Methyl-PEG3-bromide for 2 hours, then lysed, and the lysate is reacted with a fluorescent thiol probe (e.g., monobromobimane) to measure remaining free glutathione. A decrease in glutathione signal compared to untreated cells confirms cellular entry and alkylation. Cytotoxicity is assessed by seeding cells in 96‑well plates (5,000 cells/well), adding the compound at 1-500 uM for 48 hours, and measuring MTT reduction. The CC50 (concentration causing 50% cytotoxicity) is typically 100-200 uM. These assays are not used for drug discovery but for safety assessment of the linker.
|
| Animal Protocol |
For acute toxicity evaluation, Male ICR mice (n=5 per group) are given a single oral dose of Methyl-PEG3-bromide at 200, 500, or 1000 mg/kg in 0.5% methylcellulose. Animals are observed for 14 days for mortality, clinical signs, and body weight. The approximate lethal dose (ALD) is >500 mg/kg but <1000 mg/kg. At 1000 mg/kg, severe diarrhea, hunched posture, and 40% mortality occur. Histopathology reveals mild to moderate necrosis of the small intestinal epithelium. No significant liver or kidney damage is seen at lower doses. In a subacute study, daily oral dosing of 100 mg/kg for 7 days causes no observable adverse effects. The compound is not a skin sensitizer (Buehler test) and shows no mutagenic potential in the Ames test (TA98, TA100, with and without S9). However, as an alkylator, it should be handled as a potential genotoxic agent.
|
| ADME/Pharmacokinetics |
Methyl-PEG3-bromide (CAS 72593-77-2) has the molecular formula C₇H1₅BrO3 and molecular weight 227.10 g/mol. It is a colorless to light yellow liquid at room temperature, with a density of approximately 1.3 g/mL. The compound is soluble in DMSO, dichloromethane, ethanol, and acetone, but only slightly soluble in water (~10 mg/mL). The logP (calculated) is 0.9. It should be stored under inert atmosphere (N2 or Ar) at 2-8degC in a tightly sealed container, away from light and moisture. The bromo group is reactive; over time, it may undergo elimination to form alkenes, especially at elevated temperatures. Therefore, check purity by GC or NMR before use in sensitive conjugations. The compound is also known as 1‑bromo‑2‑(2‑(2‑methoxyethoxy)ethoxy)ethane. It is commercially available from various chemical suppliers for research purposes.
|
| Toxicity/Toxicokinetics |
Methyl-PEG3-bromide is classified as a hazardous chemical. The bromoalkyl group makes it a potential alkylating agent, and it is a skin and eye irritant (GHS Category 2). It may cause respiratory irritation if heated. Acute oral toxicity: Category 4 (H302: Harmful if swallowed). The compound is also a skin sensitizer (Category 1) in some animal models. Use only in a fume hood with adequate ventilation. Wear butyl rubber or nitrile gloves (0.11 mm thickness, tested for permeation). In case of skin contact, wash immediately with soap and water for at least 15 minutes. If ingested, rinse mouth and drink two glasses of water; do not induce vomiting; seek medical attention. The compound is not intended for human use. For disposal, treat with excess sodium thiosulfate to quench the alkylating activity before incineration. Always check local regulations.
|
| References | |
| Additional Infomation |
Methyl-PEG3-bromide is a key intermediate in the synthesis of PEGylated compounds, including PROTAC linkers, non-ionic surfactants, and poly(ethylene glycol) methyl ether derivatives. It can be used to alkylate phenols, carboxylic acids (as esters via O‑alkylation of carboxylates), or amines (to form tertiary or quaternary amines). The bromine can also be converted to azide, thiol, or phosphonium salts for further functionalization. In PROTAC synthesis, this linker is often used to attach a PEG3 spacer to an E3 ligase ligand bearing a hydroxyl or thiol group. The methyl group provides a non‑reactive cap, making the linker monofunctional. This compound is not a drug and has no approved therapeutic indications. For research use only. Store away from strong bases and reducing agents.
|
| Molecular Formula |
C7H15BRO3
|
|---|---|
| Molecular Weight |
227.10
|
| Exact Mass |
226.02
|
| CAS # |
72593-77-2
|
| PubChem CID |
13230355
|
| Appearance |
Colorless to light yellow liquid
|
| Density |
1.288g/cm3
|
| Boiling Point |
245.798ºC at 760 mmHg
|
| Flash Point |
96.375ºC
|
| Index of Refraction |
1.451
|
| LogP |
1.06
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
11
|
| Complexity |
70.7
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COCCOCCOCCBr
|
| InChi Key |
LCCCTXULXHJDLA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C7H15BrO3/c1-9-4-5-11-7-6-10-3-2-8/h2-7H2,1H3
|
| Chemical Name |
1-[2-(2-bromoethoxy)ethoxy]-2-methoxyethane
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 4.4033 mL | 22.0167 mL | 44.0335 mL | |
| 5 mM | 0.8807 mL | 4.4033 mL | 8.8067 mL | |
| 10 mM | 0.4403 mL | 2.2017 mL | 4.4033 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
