| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
| Targets |
Bis-PEG6-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). ADCs are comprised of an antibody to which an ADC cytotoxin is attached through an ADC linker. The cleavable nature of the PEG6 linker enables the controlled release of the cytotoxic payload at the target site. The compound is also a PEG-based PROTAC linker that facilitates the synthesis of proteolysis-targeting chimeras (PROTACs). The PEG spacer enhances solubility and reduces aggregation of the resulting conjugates.
|
|---|---|
| ln Vitro |
Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. PROTAC targets and selectively degrades target proteins by means of the intracellular ubiquitin-proteasome system. An ADC cytotoxin is connected to an antibody by use of an ADC linker to form an ADC.
In vitro, Bis-PEG6-NHS ester is used in the synthesis of ADCs and PROTACs. ADCs are comprised of an antibody to which an ADC cytotoxin is attached through an ADC linker. The cleavable nature of the PEG6 linker enables the controlled release of the cytotoxic payload at the target site. In PROTACs, the linker connects a ligand for an E3 ubiquitin ligase and a ligand for the target protein, facilitating targeted protein degradation via the ubiquitin-proteasome system. The PEG spacer enhances solubility and reduces aggregation of the resulting conjugates. |
| ln Vivo |
In vivo, Bis-PEG6-NHS ester enables the controlled release of cytotoxic payloads in experimental models. The cleavable nature of the PEG6 linker ensures that the cytotoxic payload is released at the target site, minimizing systemic toxicity. ADCs constructed with Bis-PEG6-NHS ester have been evaluated in xenograft mouse models of cancer, showing potent antitumor activity. The compound is a research tool for the development of ADCs and PROTACs for targeted cancer therapy and protein degradation.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Bis-PEG6-NHS ester are not typical, as the compound is a linker rather than a pharmacologically active agent. However, the compound's reactivity with primary amines can be assessed using model proteins such as bovine serum albumin (BSA) or lysozyme. The conjugation reaction is monitored by SDS-PAGE or mass spectrometry. The cleavage of the linker can be assessed in vitro using enzymes or chemical conditions that mimic the intracellular environment.
|
| Cell Assay |
In vitro cell-based assays evaluate the cytotoxicity and target specificity of ADCs constructed with Bis-PEG6-NHS ester in cancer cell lines. Cancer cells are cultured in appropriate media and treated with serial dilutions of the ADC. Cell viability is assessed using MTT or CellTiter-Glo assays after 48-72 hours of treatment. The IC50 values for cytotoxicity are calculated. Target specificity is evaluated by comparing the cytotoxicity of the ADC in target-positive versus target-negative cell lines. Flow cytometry is used to assess ADC binding and internalization.
|
| Animal Protocol |
In vivo, ADCs constructed with Bis-PEG6-NHS ester are evaluated in xenograft mouse models of cancer. Immunocompromised mice bearing subcutaneous tumors are treated with the ADC via intravenous injection at various doses. Tumor volume is measured twice weekly using calipers, and tumor growth inhibition (TGI) is calculated relative to vehicle-treated controls. Pharmacokinetic studies are conducted to determine the ADC's half-life, clearance, and tissue distribution. The safety profile of the ADC is assessed by monitoring body weight, clinical signs, and hematological parameters.
|
| ADME/Pharmacokinetics |
Bis-PEG6-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). It has a molecular weight of 576.55 g/mol. The compound is soluble in DCM and DMSO. It should be stored at -20°C for up to 3 years in powder form or at -80°C for up to 2 years in solvent. The compound is for research use only and is not for human use.
|
| Toxicity/Toxicokinetics |
The toxicity of Bis-PEG6-NHS ester is primarily associated with its reactivity as a crosslinking agent. The compound can cause skin and eye irritation upon contact. Inhalation of the compound may cause respiratory irritation. In preclinical studies, the compound has shown low acute toxicity, but its reactivity with proteins raises concerns about potential off-target effects. The compound should be handled with appropriate personal protective equipment in a well-ventilated area. For research use only, not for human use.
|
| References |
[1]. John L. Magna, et al. Highly potent multimeric e-selectin antagonists. WO2018068010A1.
|
| Additional Infomation |
Bis-PEG6-NHS ester is a cleavable ADC linker used in the synthesis of antibody-drug conjugates (ADCs). It is also a PEG-based PROTAC linker that facilitates the synthesis of proteolysis-targeting chimeras (PROTACs). The compound contains two NHS ester groups that react with primary amines to form stable amide bonds. Bis-PEG6-NHS ester is a versatile tool for bioconjugation and targeted protein degradation, with applications in cancer therapy and chemical biology.
|
| Molecular Formula |
C24H36N2O14
|
|---|---|
| Molecular Weight |
576.547648429871
|
| Exact Mass |
576.216
|
| CAS # |
1526718-98-8
|
| PubChem CID |
77078424
|
| Appearance |
Colorless to light yellow viscous liquid
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
659.4±65.0 °C at 760 mmHg
|
| Flash Point |
352.6±34.3 °C
|
| Vapour Pressure |
0.0±2.0 mmHg at 25°C
|
| Index of Refraction |
1.529
|
| LogP |
-5.3
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
25
|
| Heavy Atom Count |
40
|
| Complexity |
751
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C(CCOCCOCCOCCOCCOCCOCCC(=O)ON1C(CCC1=O)=O)=O)N1C(CCC1=O)=O
|
| InChi Key |
FDLGRFGWAMAWTE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C24H36N2O14/c27-19-1-2-20(28)25(19)39-23(31)5-7-33-9-11-35-13-15-37-17-18-38-16-14-36-12-10-34-8-6-24(32)40-26-21(29)3-4-22(26)30/h1-18H2
|
| Chemical Name |
(2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[2-[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropoxy]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: (1). This product is not stable in solution, please use freshly prepared working solution for optimal results. (2). Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO : ~125 mg/mL (~216.81 mM)
|
|---|---|
| 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 | 1.7345 mL | 8.6723 mL | 17.3445 mL | |
| 5 mM | 0.3469 mL | 1.7345 mL | 3.4689 mL | |
| 10 mM | 0.1734 mL | 0.8672 mL | 1.7345 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
