| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg | |||
| 5g |
|
| Targets |
As a chemical linker, this compound does not bind to biological targets. Its functional "targets" are the chemical groups on molecules to which it conjugates. In PROTAC applications, the linker connects an E3 ubiquitin ligase ligand to a target protein ligand. The azide group enables Click Chemistry reactions (CuAAc or SPAAC) with alkyne-bearing compounds. The two NHS ester groups react specifically with primary amines (e.g., lysine residues in proteins) to form stable amide bonds. The branched architecture allows for the creation of multi-functional PROTACs and bioconjugates. The PEG4 spacers improve aqueous solubility and reduce aggregation of the final conjugates.
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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 synthetic linker molecule, this compound does not exhibit pharmacological activity in cell-based assays. Its in vitro utility is demonstrated through the successful synthesis and characterization of PROTAC constructs incorporating this linker. Researchers evaluate the linker's performance by assessing conjugation efficiency (via HPLC, LC-MS, or NMR), the stability of resulting conjugates in cell culture media, and the biological activity of final PROTAC constructs in target cell lines. For PROTACs, target protein degradation is quantified by Western blot or ELISA following treatment of cells with the construct. The compound is soluble in DMSO and other organic solvents, facilitating its use in bioconjugation workflows. |
| ln Vivo |
No direct in vivo pharmacological activity is attributed to this compound. Its in vivo relevance is demonstrated through the performance of PROTAC constructs synthesized using this linker in animal models. For in vivo administration, PROTAC constructs are typically formulated in vehicles such as DMSO/PEG300/Tween-80/saline. The linker's stability in biological matrices, its contribution to the construct's pharmacokinetic profile, and its ability to maintain construct integrity are key parameters evaluated in preclinical studies. The NHS ester groups are hydrolytically unstable and would be rapidly hydrolyzed in aqueous environments, so the linker is typically used for in vitro conjugation rather than for in vivo administration as a free compound.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays are not applicable to this compound as it is a chemical linker with no intrinsic affinity for biological macromolecules. Quality control and characterization are performed using standard analytical methods. Purity is assessed by HPLC and structural integrity is confirmed by ¹H NMR, ¹³C NMR, and mass spectrometry. The azide group and NHS ester groups are verified through spectroscopic analysis. For researchers using this linker, NHS ester conjugation to primary amines is monitored by TLC, HPLC, or LC-MS. The NHS ester is moisture-sensitive and should be handled under anhydrous conditions.
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| Cell Assay |
Cell-based assays are not performed directly on this compound because it is a synthetic linker lacking biological activity. However, the biological activity of PROTAC constructs containing this linker is evaluated in relevant cell lines. Typical protocols involve treating cells with the PROTAC construct for 4-48 hours, then assessing target protein degradation by Western blot or ELISA. Cell viability, proliferation, and apoptosis are monitored using standard assays such as MTT, CCK-8, or flow cytometry. The linker's contribution to the construct's cellular uptake, stability, and efficacy is inferred from structure-activity relationship studies. DMSO stock solutions are prepared and diluted in cell culture media.
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| Animal Protocol |
In vivo animal studies are conducted with PROTAC constructs incorporating this linker, not with the linker alone. Typical protocols utilize rodent models (e.g., mice bearing tumor xenografts). The construct is administered via intravenous, intraperitoneal, or oral gavage at doses determined by preliminary pharmacokinetic and tolerability studies. Efficacy is assessed by measuring disease progression endpoints such as tumor volume, biomarker levels, or survival. Pharmacodynamic endpoints include target protein degradation in tissues (measured by Western blot or IHC) and downstream pathway modulation. The linker's stability in circulation is evaluated through plasma sampling and LC-MS/MS analysis.
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| ADME/Pharmacokinetics |
As a chemical linker, this compound does not have a conventional pharmacokinetic profile. However, the pharmacokinetic properties of PROTAC constructs incorporating this linker are evaluated in preclinical studies. Following administration in rodents, key parameters such as half-life, clearance, volume of distribution, and bioavailability are determined from plasma concentration-time data. The PEG spacers contribute to enhanced aqueous solubility, reduced protein binding, and potentially prolonged circulation time. The NHS ester groups are hydrolytically unstable and would be rapidly hydrolyzed in plasma. Linker stability in plasma is assessed by measuring intact construct concentrations over time using LC-MS/MS.
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| Toxicity/Toxicokinetics |
Standard laboratory safety precautions should be followed when handling this compound: use of personal protective equipment (gloves, safety goggles, lab coat) and handling in a well-ventilated fume hood. The NHS ester is moisture-sensitive and should be handled under anhydrous conditions. The compound should be stored at -20°C for long-term stability and protected from moisture. No genotoxicity, carcinogenicity, or reproductive toxicity data are available. The compound is not classified as a hazardous drug but should be treated with care. Researchers should consult the safety data sheet (SDS) before handling.
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| Additional Infomation |
Additional information: The compound has a CAS number of 2182601-77-8. Its molecular formula is C₄₀H₆₈N₆O₂₀ and molecular weight is approximately 953 g/mol. It is a branched PEG derivative containing an azide group and two NHS ester groups. It is a Click Chemistry reagent. It is a PEG-based PROTAC linker. It is for research use only and is not approved for clinical applications. No FDA approvals exist.
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| Molecular Formula |
C40H68N6O20
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|---|---|
| Molecular Weight |
952.996132850647
|
| Exact Mass |
952.448
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| CAS # |
2182601-77-8
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| PubChem CID |
131709294
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
-2.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
23
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| Rotatable Bond Count |
49
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| Heavy Atom Count |
66
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| Complexity |
1290
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)N(C1=O)OC(=O)CCOCCOCCOCCOCCN(CCOCCOCCOCCOCCC(=O)ON2C(=O)CCC2=O)C(=O)CCOCCOCCOCCOCCN=[N+]=[N-]
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| InChi Key |
SZQXOKLTRWLWON-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C40H68N6O20/c41-43-42-7-13-55-19-25-61-31-34-64-28-22-58-16-10-44(8-14-56-20-26-62-32-29-59-23-17-53-11-5-39(51)65-45-35(47)1-2-36(45)48)9-15-57-21-27-63-33-30-60-24-18-54-12-6-40(52)66-46-37(49)3-4-38(46)50/h1-34H2
|
| Chemical Name |
(2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethyl-[2-[2-[2-[2-[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
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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 | 1.0493 mL | 5.2466 mL | 10.4932 mL | |
| 5 mM | 0.2099 mL | 1.0493 mL | 2.0986 mL | |
| 10 mM | 0.1049 mL | 0.5247 mL | 1.0493 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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