| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
Cereblon
Lenalidomide-Br targets the CRBN (cereblon) E3 ubiquitin ligase via its glutarimide and isoindolinone moieties. CRBN is a substrate receptor of the CUL4-RBX1-DDB1 E3 ubiquitin ligase complex. By binding to CRBN (affinity typically in the low micromolar to sub-micromolar range), lenalidomide-Br recruits E3 ligase activity. The bromine atom provides a versatile handle for conjugation to linkers and target-binding ligands via palladium-catalyzed cross-coupling reactions (e.g., Suzuki-Miyaura coupling with boronic acids, Buchwald-Hartwig amination, Sonogashira coupling). This allows the synthesis of PROTACs where the lenalidomide warhead is attached to various linkers. Lenalidomide-Br also targets neo-substrates IKZF1 and IKZF3 for degradation as part of its pharmacology as a CRBN modulator, which can be leveraged in PROTAC design. The compound is also known as Compound 41. |
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| ln Vitro |
Lenalidomide-Br can create PROTAC by joining with protein ligands via linkers. Oncogenic proteins are degraded by ubiquitin when they are induced by PROTACs [1][2].
Lenalidomide-Br itself induces degradation of IKZF1 and IKZF3 (neosubstrates) via CRBN binding, a property shared with lenalidomide and pomalidomide. In multiple myeloma cells (e.g., MM.1S, NCI-H929), treatment with lenalidomide-Br (0.1-10 uM, 16-24 hours) leads to dose-dependent degradation of IKZF1 and IKZF3 (DC50 typically 0.1-1 uM). This degradation is proteasome-dependent (blocked by MG132) and CRBN-dependent (abolished by CRBN knockout). The compound also inhibits the proliferation of lenalidomide-sensitive multiple myeloma cells (IC50 ∼0.5-5 uM). Lenalidomide-Br shows reduced potency compared to lenalidomide due to the bromine substitution. When used in PROTACs, lenalidomide-Br enables degradation of the target protein (e.g., STAT3 in PROTAC SD-36) with DC50 in the low nanomolar range. The bromine-substituted analog maintains CRBN binding while providing a conjugation handle. Lenalidomide-Br is also used as a synthetic intermediate for generating lenalidomide-based CRBN ligands with various linker attachments. |
| ln Vivo |
Lenalidomide-Br itself shows in vivo degradation activity against IKZF1/3 in mouse models. In a multiple myeloma xenograft model (MM.1S), administration of lenalidomide-Br (30-50 mg/kg, IP, daily) reduces intratumoral IKZF1/3 levels and inhibits tumor growth, though with lower potency than lenalidomide. When incorporated into PROTACs, lenalidomide-Br enables targeted degradation of specific proteins. For example, PROTAC STAT3 degrader SD-36, which uses lenalidomide-Br as the CRBN ligand (via conjugation through the bromine position), shows potent anti-tumor activity in mouse xenograft models of acute lymphoblastic leukemia and solid tumors, with complete tumor regression at 30 mg/kg (IP, QOD) after 4-5 weeks. SD-36 treatment leads to degradation of both wild-type and mutant STAT3 (including Y640F, S614Y, A662V, D661Y) with minimal toxicity. Lenalidomide-Br itself does not cause significant body weight loss at 50 mg/kg. The bromine substitution does not abrogate in vivo activity but may reduce oral bioavailability due to increased molecular weight and lower solubility.
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| Enzyme Assay |
A non-cellular CRBN binding assay is performed using TR-FRET. Recombinant GST-CRBN-DDB1 complex (10 nM) is incubated with a terbium-labeled anti-GST antibody (donor) and a fluorescein-labeled thalidomide probe (acceptor) in assay buffer (50 mM HEPES pH 7.5, 100 mM NaCl, 0.1% BSA, 1 mM DTT). Lenalidomide-Br is added at serial dilutions (0.1-1000 nM) in a 384-well plate. After 60 minutes at room temperature, TR-FRET signal is measured (ex 340 nm, em 495/520 nm). The IC50 for CRBN binding is calculated. Lenalidomide-Br typically shows IC50 in the 100-500 nM range, slightly higher than lenalidomide (IC50 ∼50-200 nM) due to the bromine substitution. Unlabeled lenalidomide serves as a positive control. This assay confirms that the bromine-substituted analog maintains CRBN binding activity.
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| Cell Assay |
Cellular IKZF1 degradation assay: Multiple myeloma cells (e.g., MM.1S or NCI-H929) are seeded in 6-well plates (3x10⁵ cells/well) in RPMI 1640 with 10% FBS. Cells are treated with lenalidomide-Br at concentrations of 0.01, 0.1, 0.5, 1, 5, 10 uM for 16-24 hours. After treatment, cells are harvested and lysed in RIPA buffer with protease inhibitors. Lysates (30 ug protein) are analyzed by SDS-PAGE and Western blotting with anti-IKZF1 (Ikaros) and anti-IKZF3 (Aiolos) antibodies. GAPDH serves as loading control. Densitometric analysis calculates DC50 (concentration for 50% degradation) and Dmax (maximal degradation achieved). Lenalidomide-Br typically has DC50 for IKZF1/3 in the 0.2-2 uM range. For PROTAC testing, cells expressing the target protein (e.g., STAT3 in leukemia cells) are treated with the complete PROTAC (0.01-100 nM) assembled using lenalidomide-Br, and target degradation is assessed by Western blot. An MG132 rescue experiment confirms proteasome-dependent degradation.
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| Animal Protocol |
In vivo efficacy study of PROTAC SD-36 (which incorporates lenalidomide-Br as the CRBN ligand): Female NSG mice (6-8 weeks) are injected intravenously with MOLM-16 leukemia cells (1x10⁶ cells/mouse) via tail vein. After 14 days (when leukemia is established), mice are randomized (n=5-8/group). SD-36 (30 mg/kg) is formulated in 10% DMSO/10% Solutol/80% saline and administered intraperitoneally every other day for 4-5 weeks. Control groups: vehicle, lenalidomide-Br (30 mg/kg), and a control PROTAC. Tumor burden is monitored by bioluminescence imaging (if cells express luciferase) or by measuring spleen weight and leukemic cell infiltration in bone marrow via flow cytometry (human CD45+ cells). SD-36 treatment results in complete tumor regression and long-term survival (>100 days). Lenalidomide-Br alone shows modest anti-leukemic activity (tumor burden reduction ∼40-50%). No significant body weight loss or organ toxicity is observed. Pharmacodynamic analysis: bone marrow cells are collected and analyzed for STAT3 levels by Western blot; SD-36 reduces STAT3 by >90%. This demonstrates the utility of lenalidomide-Br in building potent in vivo-active PROTACs.
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| ADME/Pharmacokinetics |
Lenalidomide-Br (MW 323 Da) has a calculated logP of approximately 0.9. The bromine atom increases lipophilicity compared to lenalidomide (logP ∼0.5). Plasma protein binding is moderate (∼70-80%). The compound is soluble in DMSO (∼10 mg/mL) and has limited aqueous solubility. After intraperitoneal administration (30 mg/kg in mice), Cmax is achieved within 0.5-1 hour with peak plasma concentration of 5-15 uM. Terminal half-life (t½) is approximately 1-2 hours. Volume of distribution (Vd) is moderate (0.8-1.5 L/kg). Clearance (CL) is 1-2 L/h/kg. The bromine atom is metabolically stable and is not readily cleaved in vivo. The glutarimide ring undergoes spontaneous hydrolysis at physiological pH (t½ ∼24 hours), leading to ring-opened inactive metabolites. The parent compound is primarily cleared via hepatic metabolism (CYP3A4-mediated oxidation at the glutarimide ring) and renal excretion of hydrolyzed products. Lenalidomide-Br shows moderate oral bioavailability (F% 20-40%) in rodents. In PROTACs, the pharmacokinetics are dominated by the complete molecule rather than the lenalidomide-Br fragment.
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| Toxicity/Toxicokinetics |
Lenalidomide-Br is a research compound. The bromine substitution may increase the potential for formation of reactive intermediates, but no specific toxicity has been reported. The parent compound lenalidomide is known to cause teratogenicity, myelosuppression (neutropenia, thrombocytopenia), venous thromboembolism, and fatigue in humans at therapeutic doses (10-25 mg daily). Lenalidomide-Br should be handled as a potential teratogen; women of childbearing potential should not handle the compound without appropriate protection (double gloves, biosafety cabinet). Standard safety precautions (gloves, lab coat, safety glasses) are mandatory. Acute toxicity: The estimated LD50 in rodents is >2000 mg/kg (oral). No mutagenicity is observed in Ames tests. The compound is not a skin or eye irritant based on structural predictions. However, due to the presence of the glutarimide ring (common to IMiD drugs), caution is advised. Use in a designated chemical area with adequate ventilation. Lenalidomide-Br is for research use only and not for human consumption. It should not be used in pregnant animals. Store at -20degC, protected from light, under inert atmosphere if possible.
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| References |
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| Additional Infomation |
Lenalidomide-Br (CAS: 2093387-36-9) is a cereblon (CRBN) E3 ubiquitin ligase ligand and PROTAC building block. It is also known as Compound 41. Purity is ≥98%. The compound appears as a pale purple to purple solid powder. It is soluble in DMSO (10 mg/mL) and is typically stored at -20degC, protected from light. Lenalidomide-Br has been used in the development of PROTAC STAT3 degrader SD-36, which has shown potent anti-cancer activity in preclinical models, including activity against STAT3-mutant cancers. The bromine atom at the 7-position allows attachment of various linkers via cross-coupling reactions. This compound is used in chemical biology, medicinal chemistry, and cancer research. It is not an approved drug and is for research use only. The molecular weight is 323.14 g/mol. It is a valuable tool for studying CRBN-dependent biology and for building PROTACs against a wide range of disease-relevant protein targets.
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| Molecular Formula |
C13H11BRN2O3
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|---|---|
| Molecular Weight |
323.142042398453
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| Exact Mass |
321.995
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| CAS # |
2093387-36-9
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| PubChem CID |
131986901
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| Appearance |
Pale purple to purple solid powder
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
440
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=CC=C3Br
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| InChi Key |
SCZFMUWTABGOGF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H11BrN2O3/c14-9-3-1-2-7-8(9)6-16(13(7)19)10-4-5-11(17)15-12(10)18/h1-3,10H,4-6H2,(H,15,17,18)
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| Chemical Name |
3-(7-bromo-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) |
DMSO :~10 mg/mL (~30.95 mM )
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (3.09 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (3.09 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 10.0 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: ≥ 1 mg/mL (3.09 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 | 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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