| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 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, 3,4-Dibromo-Mal-PEG2-amine 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. The dibromomaleimide group reacts with thiols via Michael addition to form a stable thioether linkage. Additionally, the bromine atoms can be displaced by nucleophiles (e.g., amines, thiols) in a stepwise manner, allowing for the attachment of two different molecules (dual conjugation). The primary amine can be conjugated to a carboxylic acid-containing ligand via amide bond formation using EDC/NHS. The PEG2 spacer provides a short, hydrophilic, and flexible connection. The TFA salt improves 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 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%. The dibromomaleimide group can be characterized by its characteristic chemical shifts in NMR and by its UV absorption. The primary amine can be quantified by titration. The TFA counterion can be detected by ion chromatography.
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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 dibromomaleimide group is reacted with a thiol-containing ligand (e.g., a cysteine-containing peptide or a thiol-functionalized small molecule) via Michael addition at pH 6.5-7.5. The remaining bromine atoms can be further substituted with a second thiol-containing ligand. The primary amine is conjugated to a carboxylic acid-containing ligand (e.g., an E3 ligase ligand) via EDC/NHS. 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 short PEG2 spacer may improve the pharmacokinetic properties of the conjugate.
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| ADME/Pharmacokinetics |
This compound has a molecular weight of 524.07, a molecular formula of C12H15Br2F3N2O6, and a standard purity of ≥95%. The IUPAC name is 1-(2-(2-aminoethoxy)ethyl)-3,4-dibromo-1H-pyrrole-2,5-dione 2,2,2-trifluoroacetate. For storage, it should be kept at -20degC for up to 3 years, sealed, away from moisture and light. It is soluble in DMSO. The product should be stored under nitrogen. CAS: 2296708-07-9.
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| 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 dibromomaleimide group is reactive and should be handled with care. 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 | |
| Additional Infomation |
The 3,4-dibromomaleimide group is a versatile thiol-reactive moiety that can undergo sequential nucleophilic substitution reactions, enabling the attachment of two different thiol-containing molecules in a controlled manner. This makes it a unique tool for constructing multifunctional PROTACs or ADCs with dual payloads. The two bromine atoms can be selectively substituted by controlling the reaction conditions (e.g., pH, temperature, stoichiometry). The PEG2 spacer provides a minimal hydrophilic linker, and the primary amine allows for amide coupling to a carboxylic acid-containing ligand. This linker is a valuable building block for advanced bioconjugation and targeted protein degradation research.
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| Molecular Formula |
C12H15BR2F3N2O6
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|---|---|
| Molecular Weight |
500.060512781143
|
| Exact Mass |
499.922
|
| CAS # |
2296708-07-9
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| Related CAS # |
3,4-Dibromo-Mal-PEG2-amine;1807534-86-6
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| PubChem CID |
162640994
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
25
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| Complexity |
419
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(COCCOCCN1C(=O)C(=C(C1=O)Br)Br)N.C(=O)(C(F)(F)F)O
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| InChi Key |
MGVSSFASAOVDDG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H14Br2N2O4.C2HF3O2/c11-7-8(12)10(16)14(9(7)15)2-4-18-6-5-17-3-1-13;3-2(4,5)1(6)7/h1-6,13H2;(H,6,7)
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| Chemical Name |
1-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-3,4-dibromopyrrole-2,5-dione;2,2,2-trifluoroacetic acid
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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 Note: 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)
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| Solubility (In Vitro) |
H2O :≥ 100 mg/mL (~199.98 mM)
DMSO :~100 mg/mL (~199.98 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.00 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 (5.00 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9998 mL | 9.9988 mL | 19.9976 mL | |
| 5 mM | 0.4000 mL | 1.9998 mL | 3.9995 mL | |
| 10 mM | 0.2000 mL | 0.9999 mL | 1.9998 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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