| Size | Price | Stock | Qty |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
PEGs
No direct pharmacological target; functions as a PEG-based PROTAC linker. The bromo group serves as an alkylating handle for nucleophilic substitution (SN2) reactions, enabling conjugation to thiols, amines, or hydroxyl groups on ligands. The THP (tetrahydropyranyl) group is an acid-labile protecting group for hydroxyl functionalities. |
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| 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].
As a PROTAC linker, Br-PEG4-THP itself has no direct biological activity; its activity is realized only when incorporated into a complete PROTAC molecule. PROTACs contain two different ligands connected by a linker; one ligand binds to an E3 ubiquitin ligase (e.g., cereblon or VHL), and the other binds to the target protein of interest. Upon PROTAC binding to both proteins, the target is ubiquitinated and subsequently degraded by the proteasome. The PEG4 spacer provides flexibility, water solubility, and optimal length (approximately 16-18 Angstrom end-to-end distance), which is often ideal for achieving the correct spatial orientation between the E3 ligase and the target protein for efficient ternary complex formation and ubiquitination. |
| ln Vivo |
No direct in vivo activity. When incorporated into a PROTAC molecule, the PEG4 linker influences the in vivo pharmacokinetic properties of the PROTAC. PEG linkers improve aqueous solubility, reduce aggregation, decrease immunogenicity, and often prolong plasma circulation half-life compared to purely alkyl linkers. The PEG4 spacer is one of the most commonly used PEG linkers in PROTAC development due to its optimal balance of flexibility, polarity, and steric properties. Several clinical-stage PROTACs utilize PEG4-based linkers.
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| Enzyme Assay |
No specific assay; linker evaluation involves characterizing its structure (by NMR and mass spectrometry), purity (≥95-98% by HPLC), and reactivity (the bromo group should be >95% intact for efficient conjugation). Standard quality control parameters: molecular weight (341.24 g/mol), molecular formula (C13H2₅BrO₅), appearance (pale yellow oily matter or solid at room temperature), and boiling point (402.2 +/- 45.0degC).
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| Cell Assay |
(1) For direct cellular assays: None; the linker alone is not biologically active. (2) For PROTAC cellular assays: treat cells with a complete PROTAC synthesized using Br-PEG4-THP as the linker (0.1-1000 nM, 4-24 h). (3) Lyse cells, perform SDS-PAGE, and Western blot with antibodies against the target protein (e.g., BRD4, AR, ER, BTK, etc.). (4) Quantify degradation by densitometry normalized to loading control (GAPDH or beta-actin). (5) Assess DC50 (concentration for 50% degradation) and Dmax (maximum degradation) using nonlinear regression. (6) Assess cytotoxicity by CCK-8 or MTT assay for 48-72 h.
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| Animal Protocol |
PROTAC molecules incorporating this PEG4 linker are typically tested in murine xenograft models: (1) Use 6-8 week old female BALB/c nude mice bearing subcutaneous tumor xenografts (100-250 mm3). (2) Administer PROTAC IV (tail vein), IP, or PO (1-50 mg/kg, daily or every other day for 2-4 weeks). (3) Formulation: 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline (for IP/IV) or 0.5% methylcellulose + 0.2% Tween-80 (for PO). (4) Monitor tumor volume (caliper) and body weight twice weekly. (5) Collect tumors 4-24 h after final dose; perform Western blot for target protein degradation. (6) Measure PROTAC concentrations in plasma and tumor tissues by LC-MS/MS. (7) Perform TUNEL and IHC for Ki-67, cleaved caspase-3.
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| ADME/Pharmacokinetics |
As a linker, it contributes to the PK of conjugated PROTACs. The PEG4 spacer enhances water solubility and reduces aggregation. Standard formulation for linker handling: store at 2-8degC (or -20degC for long-term). Solubility: soluble in organic solvents (DMSO, DMF, DCM, THF, chloroform) and moderately soluble in water. For PROTAC containing PEG4 linkers: typically moderate clearance (CL ~ 10-30 mL/min/kg), moderate volume of distribution (Vd ~ 1-3 L/kg), t1/2 ~ 2-6 h (IV), oral bioavailability ~ 10-40% depending on target protein ligand. The THP protecting group can be removed under mild acidic conditions (e.g., pyridinium p-toluenesulfonate, PPTS, in ethanol or methanol, or 0.1 M HCl in THF).
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| Toxicity/Toxicokinetics |
The linker itself is generally non-toxic, but cytotoxicity is evaluated when incorporated into a complete PROTAC molecule. In vitro: CCK-8 assay on HEK293 cells with linker alone (IC50 > 200 uM). The bromo group is reactive and can alkylate biological nucleophiles if not properly conjugated, but when used as designed (consumed in linker synthesis), the final PROTAC has no free bromo group. No in vivo toxicity for linker alone. For complete PROTACs containing this linker, MTD studies are performed in rodents (typically 10-100 mg/kg, IP, daily for 14 days). Monitor body weight, clinical signs, and clinical chemistry (ALT, AST, BUN, creatinine). The product is for research use only, not for human use.
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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 |
Br-PEG4-THP is a PEG-based PROTAC linker that can be used in the synthesis of a series of PROTACs. Key features: (1) terminal bromo group provides a highly reactive alkylating handle for conjugation to thiol-, amine-, or hydroxyl-containing ligands (via SN2 nucleophilic substitution); (2) PEG4 spacer offers optimal flexibility, length (16-18 Angstrom), and hydrophilicity for PROTAC design; (3) THP (tetrahydropyranyl) group is an acid-labile protecting group for hydroxyl functionality, enabling sequential deprotection and conjugation strategies. The product is intended for research use only, not for human therapeutic or diagnostic purposes, and has not been approved by the FDA or EMA. It is commonly used in academic and industrial medicinal chemistry laboratories for the development of targeted protein degradation therapeutics.
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| Molecular Formula |
C13H25BRO5
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|---|---|
| Molecular Weight |
341.2386
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| Exact Mass |
340.088
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| CAS # |
1803547-60-5
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| PubChem CID |
156597089
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
19
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| Complexity |
194
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| Defined Atom Stereocenter Count |
0
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| SMILES |
BrC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O1
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| InChi Key |
PITHQIWYWBVVCG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H25BrO5/c14-4-6-15-7-8-16-9-10-17-11-12-19-13-3-1-2-5-18-13/h13H,1-12H2
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| Chemical Name |
2-[2-[2-[2-(2-bromoethoxy)ethoxy]ethoxy]ethoxy]oxane
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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 | 2.9305 mL | 14.6524 mL | 29.3049 mL | |
| 5 mM | 0.5861 mL | 2.9305 mL | 5.8610 mL | |
| 10 mM | 0.2930 mL | 1.4652 mL | 2.9305 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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