| Size | Price | |
|---|---|---|
| Other Sizes |
Purity: ≥98%
| Targets |
This linker does not have a biological target. Its functional groups target specific chemical moieties on other molecules. The primary amine (-NH2) reacts with carboxylic acids or activated NHS esters to form amide bonds. The t-butyl-protected carboxyl group (-COOt-Bu) can be deprotected to reveal a carboxylic acid for further conjugation. In the context of PROTACs, this linker connects the E3 ligase ligand to the target protein ligand. In ADCs, it serves as a non-cleavable spacer between the antibody and the cytotoxic payload.
|
|---|---|
| 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 selectively degrades target proteins by means of the intracellular ubiquitin-proteasome system [1]. ADC is made up of antibodies that are connected to ADC cytotoxins by an ADC linker [2].
Amino-PEG2-t-butyl ester itself does not possess intrinsic biological activity. Its activity is defined by its use as a building block to create biologically active conjugates. For example, when used to synthesize a PROTAC, the resulting molecule can induce the degradation of a target protein in cells. The PEG2 spacer ensures that the conjugate remains soluble and flexible. In vitro, the conjugation efficiency of Amino-PEG2-t-butyl ester to other molecules can be assessed by analytical techniques such as HPLC or mass spectrometry. |
| ln Vivo |
Amino-PEG2-t-butyl ester is not intended for direct in vivo administration. Its in vivo relevance is as a linker in the construction of ADCs, PROTACs, or other drug conjugates that are then administered in vivo. The PEG2 spacer in the final conjugate can influence its pharmacokinetics by increasing its solubility and reducing aggregation. The non-cleavable nature of this linker ensures that the conjugate remains intact in the bloodstream.
|
| Enzyme Assay |
Non-cellular in vitro assays for Amino-PEG2-t-butyl ester are chemical, not biological. They involve characterizing its purity and reactivity. Purity can be determined by HPLC (≥98%). Reactivity can be assessed by deprotecting the t-butyl ester with acid (e.g., TFA) and then reacting the resulting carboxylic acid with a model amine-containing compound to form an amide bond. The reaction can be monitored by LC-MS or NMR. The amine group's reactivity can be tested by reacting it with an activated NHS ester.
|
| Cell Assay |
Cellular assays are not performed with Amino-PEG2-t-butyl ester itself, but rather with the conjugates it helps create. For instance, a PROTAC synthesized using this linker can be tested in cell-based degradation assays. Cells expressing the target protein are treated with varying concentrations of the PROTAC for 6-24 hours. The levels of the target protein are then measured by Western blotting. The DC50 (concentration for 50% degradation) is determined from the concentration-response curve.
|
| Animal Protocol |
In vivo animal studies are performed with the final PROTAC or ADC synthesized using Amino-PEG2-t-butyl ester, not with the linker itself. A typical protocol involves administering the conjugate intravenously to tumor-bearing mouse models. Mice are dosed with the conjugate at various concentrations on a schedule such as once weekly for 2-3 weeks. Tumor volume and body weight are measured regularly to assess efficacy and toxicity. Pharmacodynamic markers, such as target protein levels in tumor tissue, are also evaluated.
|
| ADME/Pharmacokinetics |
Amino-PEG2-t-butyl ester is a chemical linker and does not have pharmacokinetic properties as an active drug. However, when used to create ADCs or PROTACs, the PEG2 linker influences the overall PK of the conjugate. The hydrophilic PEG spacer increases the solubility of the conjugate in aqueous media. For the linker itself, specific PK data are not available. It is typically stored as a powder at -20°C and is soluble in DMSO.
|
| Toxicity/Toxicokinetics |
Amino-PEG2-t-butyl ester is a chemical reagent for research use only and is not intended for therapeutic or diagnostic use in humans. Toxicity data for the compound itself are limited, but standard laboratory safety precautions should be followed when handling it. In the context of ADC or PROTAC development, the toxicity is primarily attributed to the cytotoxic payload or the degradation of the target protein. The compound should be stored under appropriate conditions to prevent degradation.
|
| References | |
| Additional Infomation |
Amino-PEG2-t-butyl ester (NH2-PEG2-C2-Boc) is a PEG-based PROTAC linker and a non-cleavable ADC linker. It incorporates an amino group and a t-butyl-protected carboxyl group, allowing for selective functionalization and conjugation. The hydrophilic PEG spacer increases solubility in aqueous media. It is part of a broader family of PEG-based linkers used in the synthesis of ADCs and PROTACs. The compound is commercially available and is a standard reagent in many research laboratories. It is not a drug itself and has no clinical trial or regulatory approval status.
|
| Molecular Formula |
C11H23NO4
|
|---|---|
| Molecular Weight |
233.3046
|
| Exact Mass |
233.162
|
| CAS # |
756525-95-8
|
| Related CAS # |
756525-95-8;
|
| PubChem CID |
51340927
|
| Appearance |
Colorless to light yellow liquid
|
| Density |
1.0±0.1 g/cm3
|
| Boiling Point |
313.7±22.0 °C at 760 mmHg
|
| Flash Point |
103.3±18.7 °C
|
| Vapour Pressure |
0.0±0.7 mmHg at 25°C
|
| Index of Refraction |
1.450
|
| LogP |
0.48
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
16
|
| Complexity |
189
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C(C([H])([H])C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])C([H])([H])N([H])[H])=O)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H]
|
| InChi Key |
XIVHGTLMLORWEP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C11H23NO4/c1-11(2,3)16-10(13)4-6-14-8-9-15-7-5-12/h4-9,12H2,1-3H3
|
| Chemical Name |
tert-butyl 3-[2-(2-aminoethoxy)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 |
| 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 : ≥ 100 mg/mL (~428.63 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2863 mL | 21.4316 mL | 42.8633 mL | |
| 5 mM | 0.8573 mL | 4.2863 mL | 8.5727 mL | |
| 10 mM | 0.4286 mL | 2.1432 mL | 4.2863 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
COA