| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
PEGs
PROTAC Linkers. |
|---|---|
| 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 linker molecule, endo-BCN-PEG2-NH2 itself has no intrinsic biological activity; it serves as a structural connector to join a target protein ligand and an E3 ubiquitin ligase ligand in PROTAC synthesis. The BCN group is a strained alkyne that reacts specifically and rapidly with azide groups via SPAAC without the need for a copper catalyst. This copper-free click chemistry is bioorthogonal and biocompatible, making it ideal for conjugations in the presence of cells or biological samples. The primary amine allows for conjugation to carboxylic acid-containing ligands via amide bond formation using EDC/NHS. The PEG2 spacer provides a short, hydrophilic, and flexible connection. The orthogonal functional groups enable stepwise conjugation to two different ligands. |
| ln Vivo |
No specific in vivo activity has been reported for this linker alone; its activity is derived from the final PROTAC molecule after conjugation with appropriate ligands. The in vivo efficacy of a complete PROTAC is determined in animal models.
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| Enzyme Assay |
N/A; this compound is not assessed in isolated enzyme/receptor binding assays. As a synthetic intermediate, its quality is typically confirmed by analytical methods such as HPLC and NMR, with a standard purity of ≥95%. The BCN group can be characterized by its characteristic chemical shifts in NMR (e.g., alkene protons around 5.5-6.0 ppm and bridgehead protons). The primary amine can be quantified by titration. The endo isomer can be distinguished from exo by NMR.
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| Cell Assay |
N/A; this linker is not tested alone in cell-based assays. It is used as a building block for constructing PROTACs. In a typical synthesis, the BCN group is reacted with an azide-containing ligand via SPAAC in a buffer such as PBS at room temperature for 1-2 hours. The primary amine is conjugated to a carboxylic acid-containing ligand using EDC and NHS to form an amide bond. The copper-free click chemistry avoids the potential toxicity of copper catalysts, which is particularly beneficial if the conjugation is performed in the presence of live cells. The resulting PROTAC is then tested in cells for target degradation activity.
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| Animal Protocol |
N/A; no animal studies are performed with the linker alone. For a complete PROTAC conjugate, in vivo studies are conducted following institutional guidelines. The compound is typically formulated using a vehicle containing DMSO, PEG300, Tween-80, and saline and administered via intraperitoneal (IP) or intravenous (IV) injection. The BCN group is stable under physiological conditions, making it suitable for in vivo click chemistry applications. The short PEG2 spacer may improve pharmacokinetic properties.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of 324.42, a molecular formula of C17H28N2O4, and a standard purity of ≥95%. For storage, it should be kept at -20degC for up to 3 years, sealed, away from moisture. It is soluble in DMSO and other organic solvents. The product should be protected from light. CAS: 1263166-93-3. The IUPAC name is (1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethyl (2-(2-aminoethoxy)ethyl)carbamate (endo).
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| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or veterinary use. Standard chemical safety precautions should be observed during handling. The BCN group is reactive and should be handled with care to avoid premature reaction with azides in the environment. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license. This compound is not an approved drug and has not been cleared for clinical 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 |
The endo-BCN group is one of the most reactive strained alkynes for copper-free click chemistry, with faster reaction kinetics than DBCO in many cases. This makes it ideal for rapid bioorthogonal conjugations in sensitive biological systems. The short PEG2 spacer provides a minimal hydrophilic linker that is optimal for target-E3 ligase pairs requiring a short, rigid connection. The combination of a BCN click handle and a primary amine provides orthogonal functional groups for stepwise conjugation to two different ligands. This linker is also widely used in bioconjugation, surface functionalization, and the development of targeted therapeutics and diagnostics.
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| Molecular Formula |
C17H28N2O4
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|---|---|
| Molecular Weight |
324.42
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| Exact Mass |
324.205
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| CAS # |
1263166-93-3
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| PubChem CID |
75412389
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.235
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
23
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| Complexity |
411
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1C[C@@H]2[C@@H](C2COC(=O)NCCOCCOCCN)CCC#C1
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| InChi Key |
YZGOWXGENSKDSE-XYPWUTKMSA-N
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| InChi Code |
InChI=1S/C17H28N2O4/c18-7-9-21-11-12-22-10-8-19-17(20)23-13-16-14-5-3-1-2-4-6-15(14)16/h14-16H,3-13,18H2,(H,19,20)/t14-,15+,16?
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| Chemical Name |
[(1R,8S)-9-bicyclo[6.1.0]non-4-ynyl]methyl N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]carbamate
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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) |
DMSO :~250 mg/mL (~770.61 mM)
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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 | 3.0824 mL | 15.4121 mL | 30.8242 mL | |
| 5 mM | 0.6165 mL | 3.0824 mL | 6.1648 mL | |
| 10 mM | 0.3082 mL | 1.5412 mL | 3.0824 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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