| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
PEGs
No direct pharmacological target; functions as a PROTAC linker (PEG-based linker) that joins an E3 ubiquitin ligase ligand (e.g., cereblon or VHL ligand) and a target protein ligand. It belongs to the PEG class of linkers and enhances the physicochemical properties of PROTAC molecules. |
|---|---|
| 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, Amino-PEG7-t-butyl ester itself has no direct biological activity; its activity is only realized when incorporated into a complete PROTAC molecule. PROTACs are heterobifunctional molecules containing one ligand for an E3 ubiquitin ligase and one ligand for a target protein of interest, connected by a linker. PROTACs leverage the intracellular ubiquitin-proteasome system to selectively degrade target proteins, offering a catalytic mechanism of action distinct from traditional occupancy-driven inhibitors. The PEG7 spacer provides optimal length, flexibility, and hydrophilicity to enhance the pharmacokinetic properties (solubility, stability, bioavailability) of the resulting PROTAC construct. |
| ln Vivo |
No direct in vivo activity. When incorporated into a PROTAC molecule, the PEG7 linker influences the in vivo behavior of the PROTAC. The hydrophilic PEG7 spacer reduces aggregation, increases aqueous solubility, and often reduces non-specific protein binding, leading to improved plasma stability, extended half-life, and better tissue distribution compared to alkyl linkers. The optimal linker length of PEG7 (approximately 29-31 Angstrom end-to-end distance) is often used in PROTAC design for achieving the proper spatial orientation between the E3 ligase and the target protein.
|
| Enzyme Assay |
No specific assay; linker evaluation involves characterizing its physicochemical properties (purity, molecular weight, solubility) and confirming successful conjugation. Quality control by HPLC and NMR ensures linker purity ≥95% and correct structure. The terminal amine group can react with carboxylic acids via EDC/NHS coupling to form stable amide bonds, or with activated NHS esters directly. The tert-butyl ester is a protecting group that can be removed under mild acidic conditions (e.g., TFA in DCM) to expose a free carboxyl group for additional conjugation reactions.
|
| 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 containing Amino-PEG7-t-butyl ester as the linker (0.1-1000 nM, 4-24 h). (3) Lyse cells in RIPA buffer with protease/phosphatase inhibitors. (4) Perform SDS-PAGE and Western blot with antibodies against the target protein (e.g., BRD4, AR, ER, BTK, EGFR, etc.). (5) Quantify target protein degradation by densitometry normalized to loading control (GAPDH, beta-actin, or tubulin). (6) Assess cytotoxicity by CCK-8 or MTT assay for 48-72 h.
|
| Animal Protocol |
PROTAC molecules incorporating this PEG7 linker are typically tested in murine xenograft models: (1) Use 6-8 week old female BALB/c nude mice bearing subcutaneous tumors (e.g., target protein-positive cancer cells, 150-250 mm3). (2) Administer PROTAC IV (tail vein), IP, or PO (1-50 mg/kg, daily or every other day). (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 and body weight. (5) Collect tumors 4-24 h post-last dose for Western blot to confirm target protein degradation. (6) Measure plasma and tumor PROTAC concentrations by LC-MS/MS.
|
| ADME/Pharmacokinetics |
As a linker, it contributes to the PK of conjugated PROTACs. The PEG7 spacer enhances water solubility and reduces aggregation. Standard formulation: 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline for IP/IV/IM/SC injection. Soluble in DMSO (≥ 100 mg/mL, 220.47 mM). PK of PROTACs containing this linker 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 ~ 20-50% depending on target protein ligand. For linker itself, no PK data, as it is rapidly cleared and not pharmacologically active.
|
| Toxicity/Toxicokinetics |
The linker itself is generally non-toxic, but cytotoxicity is evaluated when incorporated into a complete PROTAC molecule. In vitro: CCK-8 on HEK293 cells (IC50 > 200 uM for the linker alone). The tert-butyl ester group is hydrolyzed by esterases, releasing tert-butanol (a relatively non-toxic metabolite). No in vivo toxicity for linker alone. For complete PROTACs containing this linker, maximum tolerated dose (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.
|
| References | |
| Additional Infomation |
Amino-PEG7-t-butyl ester is a PEG-based PROTAC linker of the PEG category, may be utilized to prepare PROTAC protein degraders. The key features: (1) terminal NH2 group for conjugation to E3 ligase ligands or target protein ligands; (2) tert-butyl ester as a protecting group that can be removed under mild acid conditions (e.g., TFA in DCM) to reveal -COOH for alternative conjugation; (3) PEG7 provides optimal hydrophilicity and flexibility; (4) high purity (≥95-98%) suitable for PROTAC synthesis. This product is not approved for human use and is strictly intended for research use only in the development of targeted protein degradation therapeutics.
|
| Molecular Formula |
C21H43NO9
|
|---|---|
| Molecular Weight |
453.567427873611
|
| Exact Mass |
453.293
|
| CAS # |
2428400-07-9
|
| PubChem CID |
154730422
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
-0.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
25
|
| Heavy Atom Count |
31
|
| Complexity |
392
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C(CCOCCOCCOCCOCCOCCOCCOCCN)=O)C(C)(C)C
|
| InChi Key |
DQPAYUNKPDINFW-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H43NO9/c1-21(2,3)31-20(23)4-6-24-8-10-26-12-14-28-16-18-30-19-17-29-15-13-27-11-9-25-7-5-22/h4-19,22H2,1-3H3
|
| Chemical Name |
tert-butyl 3-[2-[2-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 | 2.2047 mL | 11.0237 mL | 22.0473 mL | |
| 5 mM | 0.4409 mL | 2.2047 mL | 4.4095 mL | |
| 10 mM | 0.2205 mL | 1.1024 mL | 2.2047 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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