| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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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, Mal-PEG2-NH2 TFA 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, or to conjugate a payload to a targeting antibody in ADC applications. The maleimide group undergoes Michael addition with thiol groups at neutral to slightly acidic pH (typically pH 6.5-7.5), forming a stable thioether linkage. This reaction is rapid and specific, making it ideal for protein conjugations. The primary amine can be conjugated to a carboxylic acid-containing ligand (e.g., a small molecule drug or a linker) via EDC/NHS activation to form an amide bond. The PEG2 spacer provides a short hydrophilic linker that reduces steric hindrance and improves water solubility. |
| ln Vivo |
No specific in vivo activity has been reported for this linker alone; its activity is derived from the final conjugate after conjugation with appropriate ligands. The in vivo efficacy of a complete PROTAC or ADC is determined in animal models.
|
| 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 ≥95-98%. The maleimide group can be characterized by its characteristic UV absorption (around 300 nm) and by the disappearance of the thiol peak upon conjugation. The TFA salt can be quantified by ion chromatography. The IUPAC name is 1-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-1H-pyrrole-2,5-dione 2,2,2-trifluoroacetate.
|
| Cell Assay |
N/A; this linker is not tested alone in cell-based assays. It is used as a building block for constructing PROTACs or ADCs. In a typical conjugation workflow for ADCs, the maleimide group is reacted with the thiol groups of reduced antibody interchain disulfides at pH 6.5-7.5 for 1-2 hours at room temperature. The primary amine (after TFA removal) can be conjugated to a carboxylic acid-containing payload (e.g., a toxin or a PROTAC warhead) via EDC/NHS activation. The resulting conjugate is then tested in cells for its biological activity, such as target degradation (for PROTACs) or cytotoxicity (for ADCs).
|
| Animal Protocol |
N/A; no animal studies are performed with the linker alone. For a complete conjugate (PROTAC or ADC), in vivo studies are conducted following institutional guidelines. The conjugate is typically formulated in a suitable vehicle (e.g., PBS for ADCs, or DMSO/PEG300/Tween-80/saline for PROTACs) and administered via intravenous (IV) injection. The PEG2 spacer may improve the pharmacokinetic properties of the conjugate by enhancing water solubility and reducing aggregation.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of 342.27, a molecular formula of C12H17F3N2O6, and a standard purity of ≥95-98%. The IUPAC name is 1-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-1H-pyrrole-2,5-dione 2,2,2-trifluoroacetate. It appears as a solid. For storage, it should be kept as a powder at -20degC for up to 3 years or in a solvent at -80degC for 6 months. It is soluble in DMSO and other organic solvents. The product should be stored in a sealed container, protected from light and moisture. The maleimide group is moisture-sensitive and should be handled under anhydrous conditions to prevent hydrolysis.
|
| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic or clinical applications. Standard chemical safety precautions should be observed during handling. The maleimide group is reactive and should be handled with care to avoid premature reaction with thiol-containing compounds. The TFA salt is hygroscopic and should be stored in a dry environment. This compound is not an approved drug and has not been cleared for clinical use.
|
| 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 |
The combination of a maleimide (thiol-reactive) and a primary amine (carboxylic acid-reactive) on a short PEG2 spacer provides a versatile bioconjugation platform. This linker is widely used in the synthesis of ADCs, where the maleimide is conjugated to antibodies and the amine is conjugated to cytotoxic payloads. In PROTAC applications, it can be used to attach a target protein ligand (via the amine) and an E3 ligase ligand (via the maleimide after conversion to a thiol). The short PEG2 spacer minimizes steric hindrance and provides a well-defined distance between the conjugated moieties. The TFA salt form improves solubility and facilitates handling.
|
| Molecular Formula |
C12H17F3N2O6
|
|---|---|
| Molecular Weight |
342.27
|
| Exact Mass |
342.104
|
| CAS # |
660843-23-2
|
| Related CAS # |
Mal-PEG2-NH2;660843-22-1
|
| PubChem CID |
71311614
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
0.174
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
23
|
| Complexity |
343
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=O)N(C1=O)CCOCCOCCN.C(=O)(C(F)(F)F)O
|
| InChi Key |
WAOHORIEWBUISG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C10H16N2O4.C2HF3O2/c11-3-5-15-7-8-16-6-4-12-9(13)1-2-10(12)14;3-2(4,5)1(6)7/h1-2H,3-8,11H2;(H,6,7)
|
| Chemical Name |
1-[2-[2-(2-aminoethoxy)ethoxy]ethyl]pyrrole-2,5-dione;2,2,2-trifluoroacetic acid
|
| 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: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
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 | 2.9217 mL | 14.6084 mL | 29.2167 mL | |
| 5 mM | 0.5843 mL | 2.9217 mL | 5.8433 mL | |
| 10 mM | 0.2922 mL | 1.4608 mL | 2.9217 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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