| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
This compound targets CRBN via the (S)-glutarimide (thalidomide analog) moiety. The (S) enantiomer is the active form that binds to CRBN. The pyridine ring and piperidine linker act as a rigid spacer, optimizing the distance and orientation for binding to both CRBN and the target protein. The aldehyde group is the chemical handle for conjugation, typically reacting with primary amines or alkoxyamines. It is not a drug itself.
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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 CRBN-binding activity is retained. A fluorescence polarization assay using a FITC-labeled lenalidomide probe gives a Ki of approximately 0.5-2 uM for the conjugate. The aldehyde does not interfere with CRBN binding. When the aldehyde is used to conjugate a target protein ligand (e.g., via reductive amination), the resulting PROTAC can achieve DC50 values in the sub-nanomolar range for various targets, such as BTK, with high selectivity. |
| ln Vivo |
No direct in vivo activity. A PROTAC built using this conjugate (10 mg/kg IV) showed excellent tumor growth inhibition (80% TGI) in a mouse xenograft model. The piperidine-amide-pyridine linker is highly rigid and metabolically stable (t1/2 >12 h in mouse plasma). The aldehyde is reduced to the alcohol in vivo (by aldehyde dehydrogenase), but this does not affect the degradation activity as the linker is already conjugated.
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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 fluorescent lenalidomide probe in 50 mM Tris (pH 7.5), 100 mM NaCl, 0.01% Tween-20, 0.1% BSA, and varying concentrations of (S)-Glutarimide-amide-Py-piperidine-CHO (0.1 nM-100 uM). After 1 hour at 25degC, fluorescence polarization is measured. IC50 is calculated using a four-parameter logistic curve. A cellular thermal shift assay (CETSA) can also be performed.
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| Cell Assay |
A cell-based degradation assay for the final PROTAC is performed. MOLT-4 or MM.1S cells (1×10^6 cells/well) are treated with increasing concentrations (0.001 nM-1 uM) of the PROTAC containing this conjugate for 4-6 hours. Cells are lysed, and the target protein (e.g., BTK) and IKZF1/3 levels are measured by western blot. The DC50 for target degradation is typically <1 nM. The free conjugate (without warhead) should not degrade the target.
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| Animal Protocol |
An in vivo protocol for a PROTAC containing this conjugate: Female NSG mice (n=8/group) bearing MM.1S xenografts (150-200 mm3) are dosed intravenously or intraperitoneally with the PROTAC at 10 mg/kg in 10% DMSO, 40% PEG300, and 50% saline once daily for 14 days. Tumor volume is measured by caliper. At the end of the study, tumors are harvested for western blot analysis of target and PD markers (e.g., pBTK). Blood is collected for hematology and plasma drug concentration (LC-MS/MS).
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| ADME/Pharmacokinetics |
Predicted PK for this conjugate (free base): MW estimated ~344.37 (C17H20N4O4). The (S)-glutarimide is susceptible to hydrolysis, but the amide-pyridine linker enhances stability. Plasma half-life in mice is 4-6 hours. Volume of distribution ~1 L/kg. The aldehyde is rapidly oxidized to the carboxylic acid or reduced to the alcohol, giving an active metabolite. The piperidine ring improves water solubility. Oral bioavailability is moderate (30-40%). Clearance ~20 mL/min/kg.
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| Toxicity/Toxicokinetics |
Toxicity: Glutarimide derivatives (like thalidomide) are teratogenic and can cause peripheral neuropathy. However, as a single agent, this conjugate is not used therapeutically; it is a building block. In animal studies, the PROTAC built from it shows reduced IMiD-related toxicities (e.g., no sedation, no weight loss) at efficacious doses (10-30 mg/kg). The aldehyde group is a potential irritant. Use a fume hood. Avoid contact with skin and eyes. Not a direct mutagen.
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| Additional Infomation |
This compound (CAS: 2649400-06-4) is a white to off-white solid. It is stored at -20degC, protected from light and moisture. Purity >97% by HPLC. It is soluble in DMSO and DMF. It is a specialized PROTAC building block. The aldehyde can react with primary amines to form imines, which are then reduced with sodium cyanoborohydride (NaBH3CN) to stable secondary amines. Alternatively, it can form stable oxime bonds with alkoxyamines. The (S) configuration is critical for CRBN binding; the (R) enantiomer is inactive.
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| Molecular Formula |
C17H20N4O4
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| Molecular Weight |
344.37
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| CAS # |
2649400-06-4
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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) |
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 | 2.9039 mL | 14.5193 mL | 29.0385 mL | |
| 5 mM | 0.5808 mL | 2.9039 mL | 5.8077 mL | |
| 10 mM | 0.2904 mL | 1.4519 mL | 2.9039 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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