| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
5-Br-6-F-Desamino lenalidomide binds cereblon (CRBN), the substrate receptor of the CRL4 E3 ubiquitin ligase complex, via its glutarimide ring. The halogen substituents modulate binding affinity and neosubstrate selectivity.
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| ln Vitro |
PROTAC contains two distinct ligands linked by a single linker: one is the ligand for the E3 ubiquitin ligase, and the other is the ligand for the target protein. PROTAC utilizes the intracellular ubiquitin-proteasome system to selectively degrade the target protein.
In vitro, this compound serves as a CRBN-binding warhead. Its CRBN binding affinity can be measured by SPR or FP. When conjugated via a linker to a target protein ligand, the resulting PROTAC facilitates ubiquitination and degradation of the target protein in cell-free and cell-based assays. The desamino modification may reduce off-target degradation of IKZF1/3. |
| ln Vivo |
In vivo, complete PROTACs incorporating this ligand induce CRBN-dependent degradation of target proteins in animal models (e.g., xenograft mice). The ligand alone has no degradation activity. The halogens may improve metabolic stability.
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| Enzyme Assay |
CRBN binding affinity is measured using recombinant CRBN-DDB1 complex. Fluorescence polarization competition assay with a fluorescent CRBN probe. SPR with immobilized CRBN-DDB1 gives ka, kd, Kd. IC50 determined. The halogens may increase binding affinity compared to lenalidomide.
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| Cell Assay |
Cell-based evaluation: target-expressing cells are treated with PROTAC (0.01 nM-10 microM, 4-24 h), lysed, and analyzed by Western blot for target degradation. DC50 and Dmax calculated. CRBN dependence confirmed by lenalidomide competition. Proteasome dependence confirmed by MG132.
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| Animal Protocol |
Animal studies: xenograft mice (100-200 mm3 tumors) randomized (n=6-10). PROTAC formulated in vehicle, administered IP/PO QD/Q2D at 1-30 mg/kg for 14-28 days. Tumor volume and body weight monitored. At endpoint, tumors harvested for immunoblot and IHC to assess target knockdown.
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| ADME/Pharmacokinetics |
No PK data for isolated ligand; PK determined by final PROTAC. The glutarimide ring is hydrolytically labile. The bromine and fluorine are metabolically stable. Typical PROTAC PK: IV t1/2 2-8 h, CL 10-30 mL/min/kg, Vd 1-3 L/kg; PO bioavailability 5-30%.
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| Toxicity/Toxicokinetics |
Toxicity for isolated ligand not reported. For final PROTAC: monitor body weight, clinical signs, serum chemistry, hematology, histopathology. CRBN ligands may cause off-target degradation of IKZF1/3 (neutropenia/thrombocytopenia). The desamino and halogen modifications may reduce this. Proteomics for off-target identification.
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| Additional Infomation |
5-Br-6-F-Desamino lenalidomide, CAS 2409005-96-3, is a research-use CRBN ligand for PROTACs. The halogens provide synthetic handles and modulate properties.
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| Molecular Formula |
C13H10BRFN2O3
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|---|---|
| Molecular Weight |
341.14
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| Exact Mass |
339.986
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| CAS # |
2409005-96-3
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| PubChem CID |
146300188
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
20
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| Complexity |
473
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)NC(=O)C1N2CC3=CC(=C(C=C3C2=O)F)Br
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| InChi Key |
JBSWVRQPSOANFC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H10BrFN2O3/c14-8-3-6-5-17(13(20)7(6)4-9(8)15)10-1-2-11(18)16-12(10)19/h3-4,10H,1-2,5H2,(H,16,18,19)
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| Chemical Name |
3-(6-bromo-5-fluoro-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione
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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) |
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
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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 | 2.9313 mL | 14.6567 mL | 29.3135 mL | |
| 5 mM | 0.5863 mL | 2.9313 mL | 5.8627 mL | |
| 10 mM | 0.2931 mL | 1.4657 mL | 2.9313 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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