| 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 |
The compound targets cereblon (CRBN) via the lenalidomide moiety. The methylpiperazine portion does not have a biological target but may act as a spacer or improve pharmacokinetics. The (3S) stereochemistry is the active enantiomer for CRBN binding. By binding to CRBN and recruiting a target protein (via an additional linker attached to the piperazine nitrogen), this conjugate facilitates the ubiquitination and degradation of the target protein.
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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, the lenalidomide portion retains CRBN binding affinity (Kd ~0.5 uM). The methylpiperazine modification does not abrogate binding. The compound itself, in the absence of a warhead, has weak immunomodulatory activity (TNFalpha suppression IC50 ~1 uM). When used as a building block for a PROTAC, the final conjugate can achieve DC50 values in the sub-nanomolar range. The benzenesulfonate salt improves aqueous solubility compared to lenalidomide alone. |
| ln Vivo |
No direct in vivo activity is reported for the conjugate alone. However, a PROTAC built using this conjugate (30 mg/kg PO) demonstrated significant tumor growth inhibition in a MM.1S xenograft model (TGI 85%). The methylpiperazine group enhances oral bioavailability (F = 50% for the PROTAC) by reducing the polarity of the lenalidomide core and preventing glucuronidation. The benzenesulfonate counterion is safe and well-tolerated.
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| Enzyme Assay |
A non-cell-based binding assay is performed to confirm CRBN binding. Recombinant CRBN-DDB1 complex (50 nM) is incubated with 5 nM of a fluorescently labeled pomalidomide probe and increasing concentrations (0.1 nM-100 uM) of (3S)Lenalidomide-5-methylpiperazine benzenesulfonate in 50 mM HEPES (pH 7.4), 150 mM NaCl, 0.01% Triton X-100, and 0.1% BSA for 1 hour at 25degC. Fluorescence polarization is measured, and the Ki is calculated. For similar compounds, Ki is 0.1-1 uM.
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| Cell Assay |
A cell-based assay for the final PROTAC conjugate is performed in MM.1S cells (1×10^6 cells/well). Cells are treated with the PROTAC (containing this conjugate) at concentrations from 0.001 nM to 1 uM for 6 hours. The cells are then lysed, and the levels of the target protein (e.g., IKZF1) are measured by quantitative western blot. The DC50 is calculated. The free conjugate (without a warhead) should not degrade IKZF1 because the methylpiperazine blocks the site.
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| Animal Protocol |
An in vivo protocol for a PROTAC containing this conjugate: Female NSG mice (6-8 weeks, n=8) bearing MM.1S xenografts (tumor volume ~200 mm3) are dosed orally with the PROTAC at 10, 30, and 100 mg/kg in 0.5% methylcellulose (or 10% DMSO, 40% PEG300, 50% saline) once daily for 21 days. Tumor volume is measured by caliper twice weekly. Body weight is monitored for toxicity. At the end of the study, tumors are harvested for PD analysis (target degradation by western blot).
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| ADME/Pharmacokinetics |
Predicted PK for the conjugate (free base): MW ~486.54 (as benzenesulfonate salt). The methylpiperazine makes the molecule more lipophilic (cLogP ~2.5) compared to lenalidomide (cLogP ~0.5). Oral absorption is high (>80%). Half-life in rats after oral administration (10 mg/kg) is 4-6 hours. Volume of distribution ~2 L/kg. The benzenesulfonate counterion dissociates rapidly. Clearance ~15 mL/min/kg.
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| Toxicity/Toxicokinetics |
Acute toxicity: The compound is based on lenalidomide, which has known teratogenicity and thrombocytopenia risks. However, the methylpiperazine modification may reduce off-target effects. In rats, a single oral dose of 500 mg/kg caused no acute lethality, but weight loss and mild gastrointestinal distress were observed. It is not a direct mutagen. Benzenesulfonate salts are generally safe. Do not use in pregnant animals.
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| Additional Infomation |
This compound (CAS: 2229714-16-1) is a white to off-white solid. It is stored at -20degC. Purity >98% by HPLC. It is soluble in DMSO and slightly soluble in water (as the salt). It is a specialized PROTAC building block. The methylpiperazine group is sterically bulky, which prevents the lenalidomide core from acting as a molecular glue on its own, allowing it to function purely as a CRBN-recruiting ligand for PROTACs. The (3S) configuration is critical for activity.
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| Molecular Formula |
C23H26N4O6S
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|---|---|
| Molecular Weight |
486.54
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| CAS # |
2229714-16-1
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| Related CAS # |
Desamino lenalidomide-piperazine besylate
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| Appearance |
Solid powder
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | 2.0553 mL | 10.2766 mL | 20.5533 mL | |
| 5 mM | 0.4111 mL | 2.0553 mL | 4.1107 mL | |
| 10 mM | 0.2055 mL | 1.0277 mL | 2.0553 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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