| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
Bromo-PEG1-C2-azide functions as a PEG-based linker in PROTACs, connecting a target protein ligand to an E3 ubiquitin ligase ligand. The bromide group serves as a handle for nucleophilic substitution reactions, enabling the attachment of the linker to thiol- or amine-functionalized ligands. The azide group allows for the conjugation of the linker to alkyne-functionalized ligands via click chemistry. The short PEG spacer provides flexibility and hydrophilicity, improving the solubility of the final conjugate.
|
|---|---|
| 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].
In vitro, Bromo-PEG1-C2-azide is used in the synthesis of PROTACs that demonstrate potent degradation of target proteins. The bifunctional nature of the linker allows for the sequential or simultaneous conjugation of two different ligands. The bromide group can be displaced by a nucleophile on one ligand, while the azide group can be conjugated to an alkyne on the other ligand via click chemistry. The short PEG spacer provides optimal spacing and flexibility for the formation of the ternary complex. |
| ln Vivo |
In vivo, Bromo-PEG1-C2-azide-based PROTACs have the potential to demonstrate improved pharmacokinetic properties due to the PEG spacer. The hydrophilic PEG chain helps to reduce aggregation and nonspecific protein binding. However, the short length of the PEG1 spacer may limit the flexibility and solubility enhancement compared to longer PEG linkers. The in vivo efficacy of PROTACs containing this linker would depend on the specific target and the overall properties of the molecule.
|
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Bromo-PEG1-C2-azide involve evaluating the binding affinity of the complete PROTAC molecule to its target protein and the E3 ligase. Surface plasmon resonance (SPR) or biolayer interferometry (BLI) is used to measure the binding kinetics. The click chemistry conjugation of the azide group to alkyne-functionalized ligands is confirmed by mass spectrometry or NMR. The bromide group's reactivity with nucleophiles is confirmed by the formation of the desired conjugate.
|
| Cell Assay |
In vitro cellular experiments for Bromo-PEG1-C2-azide-based PROTACs are performed to evaluate target protein degradation. Cells are treated with varying concentrations of the PROTAC, and the levels of the target protein are quantified by Western blot. The DC50 and Dmax values are calculated from dose-response curves. To confirm that degradation is mediated by the ubiquitin-proteasome system, cells are co-treated with a proteasome inhibitor such as MG132.
|
| Animal Protocol |
In vivo animal studies for Bromo-PEG1-C2-azide-based PROTACs are conducted using xenograft or transgenic mouse models. The PROTAC is administered via intravenous, intraperitoneal, or oral routes at various doses. Target protein degradation in tissues is assessed by Western blot or immunohistochemistry. Pharmacodynamic markers downstream of the target protein are also measured.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Bromo-PEG1-C2-azide-based PROTACs are influenced by the short PEG spacer. The PEG chain provides some hydrophilicity, but the short length may limit the reduction in renal clearance and the prolongation of half-life. The overall pharmacokinetic profile would depend on the specific properties of the complete PROTAC molecule.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Bromo-PEG1-C2-azide-based PROTACs is generally favorable due to the biocompatibility of PEG. However, the bromide group may react with nucleophiles in biological systems, potentially leading to off-target effects. In preclinical studies, toxicity is assessed by monitoring body weight, clinical signs, and histopathological changes in major organs.
|
| 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
|
| Additional Infomation |
Bromo-PEG1-C2-azide is a bifunctional PEG-based linker used in bioconjugation and PROTAC synthesis. It contains a terminal bromide and an azide group. The bromide group allows for nucleophilic substitution reactions, while the azide group enables click chemistry conjugation. This linker is a valuable tool for the synthesis of PROTACs and other bifunctional molecules, providing flexibility and hydrophilicity.
|
| Molecular Formula |
C₄H₈BRN₃O
|
|---|---|
| Molecular Weight |
194.03
|
| Exact Mass |
192.985
|
| CAS # |
1144106-65-9
|
| PubChem CID |
129984731
|
| Appearance |
Colorless to light yellow liquid
|
| LogP |
1.7
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
9
|
| Complexity |
102
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(COCCBr)N=[N+]=[N-]
|
| InChi Key |
SBVSTNMRZMYOGF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C4H8BrN3O/c5-1-3-9-4-2-7-8-6/h1-4H2
|
| Chemical Name |
1-azido-2-(2-bromoethoxy)ethane
|
| Synonyms |
BromoPEG1C2azide; Bromo PEG1 C2 azide
|
| 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 |
| 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 | 5.1538 mL | 25.7692 mL | 51.5384 mL | |
| 5 mM | 1.0308 mL | 5.1538 mL | 10.3077 mL | |
| 10 mM | 0.5154 mL | 2.5769 mL | 5.1538 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
