PEGs

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].

Absorption, Distribution and Excretion
…It can be absorbed through the skin… …This substance can be absorbed through rabbit skin up to toxic doses… To assess the hazards of skin contact with specific undiluted glycol ethers, we determined their absorption in vitro on isolated human abdominal epidermis. Epidermal membranes were placed in a glass diffusion cell, and after preliminary determination of their permeability to tritized water, excess undiluted glycol ether was applied to the outer surface of the epidermis for 8 hours. The content of glycol ether in the aqueous receptors on the subepidermal side was quantitatively analyzed using gas chromatography. The final determined tritized water permeability was compared with the initial value to determine whether glycol ether contact caused any irreversible alteration of epidermal barrier function. 2-Methoxyethanol (EM) was most readily absorbed (mean stable absorption rate of 2.82 mg/cm²/hr), and 1-methoxyprop-2-ol (PM) also had a relatively high absorption rate (1.17 mg/cm²/hr). The absorption rates of monoethylene glycol ethers (EM, 2.82 mg/cm²/hr; 2-ethoxyethanol, EE, 0.796 mg/cm²/hr; 2-butoxyethanol, EB, 0.198 mg/cm²/hr) and diethylene glycol compounds (2-(2-methoxyethoxy)ethanol, DM, 0.206 mg/cm²/hr) all decreased with increasing molecular weight or decreasing volatility. The absorption rates of 2-(2-ethoxyethoxy)ethanol (DE, 0.125 mg/cm²/hr) and 2-(2-butoxyethoxy)ethanol (DB, 0.035 mg/cm²/hr) were also observed. Ethyl 2-ethoxyethyl (EEAc) showed a similar absorption rate to its parent alcohol EE. The absorption rates of diethylene glycol ethers were lower than their corresponding monoethylene glycol equivalents. The combination of intrinsic toxicity and dermal absorption capacity helps assess the hazards of exposure to undiluted glycol ethers. The toxicity of bis(2-methoxyethyl) ethers was studied in rats. Male Sprague-Dawley rats were orally administered 0.051 or 5.1 mmol/kg (14)C-labeled bis(2-methoxyethyl) ether. The major metabolites in urine were (2-methoxyethoxy)acetic acid and methoxyacetic acid, accounting for approximately 70% and 6% of the administered dose, respectively. Small amounts of N-(methoxyacetyl)glycine, diethylene glycol, 2-methoxyethanol, and 2-(2-methoxyethoxy)ethanol were also detected. Only unmetabolized bis(2-methoxyethyl) ether was detected in the volatile organic compounds of exhaled breath. Furthermore, rats were administered up to 5.1 mmol/kg of 2-(2-methoxyethoxy)ethanol or (2-methoxyethoxy)acetic acid daily for up to 20 times daily from day 3 to day 21. Neither 2-(2-methoxyethoxy)ethanol nor (2-methoxyethoxy)acetic acid caused any gross or histopathological changes in the testes. Metabolism of bis(2-methoxyethyl) ether occurs primarily via O-demethylation, followed by oxidation to (2-methoxyethoxy)acetic acid. 2-(2-methoxyethoxy)ethanol and (2-methoxyethoxy)acetic acid lack toxicity, suggesting that the testicular toxicity of bis(2-methoxyethyl) ether may be attributed to its minor metabolite, methoxyacetic acid. Metabolism/Metabolites…Male Sprague-Dawley rats were orally administered 0.051 or 5.1 mmol/kg of 14C-labeled bis(2-methoxyethyl) ether. The major metabolites in urine were (2-methoxyethoxy)acetic acid and methoxyacetic acid, accounting for approximately 70% and 6% of the administered dose, respectively. Small amounts of N-(methoxyacetyl)glycine, diethylene glycol, 2-methoxyethanol, and 2-(2-methoxyethoxy)ethanol were detected. Only unchanged bis(2-methoxyethyl) ether was detected in the volatile organic compounds of exhaled breath. The metabolism of bis(2-methoxyethyl) ether primarily occurs via O-demethylation, followed by oxidation to (2-methoxyethoxy)acetic acid. The lack of toxicity in 2-(2-methoxyethoxy)ethanol and (2-methoxyethoxy)acetic acid suggests that the testicular toxicity of bis(2-methoxyethyl) ether may originate from its secondary metabolite, methoxyacetic acid.

Toxicity Data
LC (Rats) > 2,000 mg/m³/1h

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Non-human Toxicity Values Oral LD50 (Rats): 5500 mg/kg body weight Oral LD50 (Rats): 6310 mg/kg body weight Intraperitoneal LD50 (Rats): 2722 mg/kg body weight Intraperitoneal LD50 (Rats): 3000 mg/kg body weight For more complete non-human toxicity data on diethylene glycol monomethyl ethers (12 in total), please visit the HSDB record page.

[1]. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562.

Diethylene glycol monomethyl ether is a colorless liquid with a sweet taste. It floats on water and is miscible with water. (USCG, 1999)
2-(2-methoxyethoxy)ethanol is a hydroxyl polyether, a monomethyl ether derivative of diethylene glycol. It is both a teratogen and a solvent. It is a hydroxyl polyether, diether, and ethylene glycol ether. It is functionally related to diethylene glycol.
2-(2-methoxyethoxy)ethanol has been reported in tomatoes (Solanum lycopersicum), and relevant data exist.
Therapeutic Uses

Experimental Study: This study used a male Fischer rat leukemia transplantation model to conduct a structure-activity relationship study on nine ethylene glycol alkyl ethers to assess their effects on tumor progression in transplant recipients. The chemicals were added to drinking water concurrently with the transplantation surgery and continued to be added throughout the study. A total of 20 million leukemia cells were subcutaneously injected into syngeneic rats. After 60 days, the relative weight of the spleen increased tenfold, the white blood cell count increased 100fold, and the red blood cell index and platelet count decreased by 50%. Adding 2.5 mg/mL of ethylene glycol monomethyl ether to drinking water completely eliminated all clinical, morphological, and histopathological evidence of leukemia, while the same dose of ethylene glycol monoethyl ether reduced these responses by approximately 50%. Seven ethylene glycol ether compounds were ineffective as anti-leukemia drugs, including ethylene glycol, monopropyl ethylene glycol ether, monobutyl ethylene glycol ether, monophenyl ethylene glycol ether, diethylene glycol, and monomethyl diethylene glycol ether and monoethyl diethylene glycol ether.
Drug Warning
Retrovena cava ureter is a very rare disease.
Based on experimental studies, one possible cause is maternal exposure to diethylene glycol monomethyl ether or ethylene glycol monomethyl ether. This article reports a case of cardiovascular, skeletal, and posterior ureteral malformations caused by the mother's exposure to the aforementioned substances while working in a textile factory.

C5H12O3

120.15

120.078

111-77-3

8134

Colorless to light yellow liquid

1.0±0.1 g/cm3

194.1±0.0 °C at 760 mmHg

−70 °C(lit.)

83.9±0.0 °C

0.1±0.8 mmHg at 25°C

1.413

-1.16

1

3

5

8

38.7

0

SBASXUCJHJRPEV-UHFFFAOYSA-N

InChI=1S/C5H12O3/c1-7-4-5-8-3-2-6/h6H,2-5H2,1H3

2-(2-methoxyethoxy)ethanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)