| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
Cereblon
CRBN (cereblon), an E3 ubiquitin ligase. |
|---|---|
| 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[2].
As a cereblon-binding ligand, Lenalidomide-5-Br itself has no intrinsic degradation activity; its function is to bind to cereblon and recruit the E3 ubiquitin ligase complex. The bromine atom at the 5-position can be used for cross-coupling reactions (e.g., Suzuki-Miyaura with boronic acids, Ullmann coupling with amines) to attach a linker or a target protein ligand directly. When conjugated to a target protein ligand via a linker, the resulting PROTAC can simultaneously bind to both a target protein and cereblon, leading to ubiquitination and subsequent proteasomal degradation of the target protein. The 5-position conjugation site may preserve the binding affinity of the lenalidomide core for cereblon better than modifications at the glutarimide nitrogen, which can interfere with binding. |
| ln Vivo |
No specific in vivo activity has been reported for this ligand alone; its in vivo degradation activity is observed only when conjugated to a target protein ligand to form a complete PROTAC molecule. The in vivo efficacy of such a PROTAC is typically evaluated in animal models of target-driven diseases.
|
| Enzyme Assay |
N/A; as a ligand, its binding affinity to cereblon is typically determined using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) as part of the validation of the final PROTAC construct. The compound is used as a synthetic intermediate. The purity of the compound is typically confirmed by HPLC, with a standard purity of ≥98%. The bromine atom can be characterized by its characteristic isotopic pattern in mass spectrometry and by its chemical shift in NMR spectroscopy.
|
| Cell Assay |
N/A; this ligand is not evaluated alone in cell-based assays but is used as a building block to construct cereblon-recruiting PROTACs. In a typical functionalization step, the bromine atom is reacted with a boronic acid-containing linker or target ligand via Suzuki-Miyaura cross-coupling using a palladium catalyst. The resulting PROTAC is then tested in target-expressing cancer cells for degradation activity by Western blotting to determine the DC50 (half-maximal degradation concentration). The 5-position conjugation site allows for diverse PROTAC structures that are not accessible via standard amide coupling at the glutarimide nitrogen.
|
| Animal Protocol |
N/A; no animal studies are performed with the ligand alone. In vivo efficacy studies would be conducted using the complete PROTAC molecule synthesized from this building block. The PROTAC would be formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered to animal models via intraperitoneal (IP) or intravenous (IV) injection.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of approximately 323.15, a molecular formula of C13H11BrN2O3, and a standard purity of ≥98%. The IUPAC name is 3-(5-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione. It appears as a solid powder. For storage, it should be kept as a powder at -20degC for up to 3 years or at 4degC for up to 2 years, sealed, away from moisture. In a solvent, it can be stored at -80degC for 6 months or at -20degC for 1 month. It is soluble in DMSO. CAS: 1010100-26-1.
|
| Toxicity/Toxicokinetics |
This product is for research use only and is not for human therapeutic or clinical applications. Standard chemical safety precautions should be followed during handling. The product has not been fully validated for medical applications. It is not an approved therapeutic drug and has not been cleared for clinical use. Lenalidomide is an immunomodulatory drug (IMiD) clinically used for multiple myeloma and myelodysplastic syndromes; this derivative is for research purposes only.
|
| References | |
| Additional Infomation |
The bromine atom at the 5-position of the isoindole ring provides a versatile handle for cross-coupling reactions, enabling the attachment of linkers and target ligands via carbon-carbon bond formation. This alternative conjugation site may be advantageous for PROTACs where attachment at the glutarimide nitrogen reduces binding affinity to cereblon. The 5-position conjugation site has been used in the development of PROTACs targeting various proteins, including IRAK4 and BET proteins. This compound is also known as 3-(5-bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione and is a valuable building block for developing cereblon-recruiting PROTACs with novel linker attachment strategies.
|
| Molecular Formula |
C13H11BRN2O3
|
|---|---|
| Molecular Weight |
323.14
|
| Exact Mass |
321.995
|
| CAS # |
1010100-26-1
|
| PubChem CID |
69049011
|
| Appearance |
Off-white to gray solid powder
|
| Density |
1.688±0.06 g/cm3
|
| Boiling Point |
587.6±50.0 °C
|
| LogP |
0.9
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
19
|
| Complexity |
440
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
BrC1C([H])=C([H])C2C(N(C([H])([H])C=2C=1[H])C1([H])C(N([H])C(C([H])([H])C1([H])[H])=O)=O)=O
|
| InChi Key |
CMRQAKJTXKOGSF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C13H11BrN2O3/c14-8-1-2-9-7(5-8)6-16(13(9)19)10-3-4-11(17)15-12(10)18/h1-2,5,10H,3-4,6H2,(H,15,17,18)
|
| Chemical Name |
3-(6-bromo-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione
|
| 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 :~12.5 mg/mL (~38.68 mM )
H2O :< 0.1 mg/mL |
|---|---|
| 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 | 3.0946 mL | 15.4732 mL | 30.9463 mL | |
| 5 mM | 0.6189 mL | 3.0946 mL | 6.1893 mL | |
| 10 mM | 0.3095 mL | 1.5473 mL | 3.0946 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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