| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| Targets |
Thalidomide-NH-C5-NH2 TFA targets the cereblon (CRBN) protein, which is a substrate receptor of the E3 ubiquitin ligase complex. The thalidomide-based pharmacophore binds to CRBN with high affinity, recruiting the E3 ubiquitin ligase machinery. The C5 alkyl linker provides a 5-carbon spacer, and the terminal primary amine serves as a conjugation handle for attachment to target protein ligands via amide bond formation using standard coupling chemistry. This conjugate is designed for one-step PROTAC assembly, where the amine reacts with a carboxylic acid-containing target protein ligand.
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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.
Thalidomide-NH-C5-NH2 TFA does not have independent in vitro activity as it is a ligand-linker conjugate rather than a complete PROTAC. Its biological activity is evaluated after conjugation to a target protein ligand to form a full PROTAC. For the resulting PROTAC, standard cellular assays involve treating target cells with the PROTAC and measuring target protein degradation by western blotting. The CRBN-binding thalidomide moiety ensures efficient recruitment of the E3 ubiquitin ligase complex, leading to ubiquitination and proteasomal degradation of the target protein. |
| ln Vivo |
No direct in vivo activity has been reported for Thalidomide-NH-C5-NH2 TFA alone. When conjugated to a target protein ligand to form a PROTAC, the compound enables targeted protein degradation in vivo. Standard in vivo protocols for PROTACs incorporating this conjugate involve administration to tumor-bearing mice (typically via intraperitoneal or intravenous injection at doses of 1-50 mg/kg). The CRBN ligand ensures recruitment of endogenous CRBN E3 ligase machinery, leading to ubiquitination and proteasomal degradation of the target protein. The C5 linker length provides optimal spacing for ternary complex formation.
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| Enzyme Assay |
No specific enzyme/receptor binding protocols have been established for this ligand-linker conjugate alone. Standard binding assays for the thalidomide-based CRBN ligand component involve surface plasmon resonance (SPR) or fluorescence polarization to measure direct binding affinity (KD) to the cereblon protein. For PROTAC synthesis, the terminal primary amine of Thalidomide-NH-C5-NH2 TFA is conjugated to a carboxylic acid-containing target protein ligand using standard amide coupling conditions. Typically, the target protein ligand (1.0-1.5 equivalents) is dissolved in DMF or DMSO with HATU or HBTU (1.2-1.5 equivalents) and DIPEA (2-3 equivalents). The amine-containing conjugate is then added and stirred at room temperature for 12-24 hours. The resulting PROTAC is purified by preparative HPLC and characterized by LC-MS.
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| Cell Assay |
Thalidomide-NH-C5-NH2 TFA is not evaluated in cellular assays alone. For cellular evaluation of PROTACs synthesized using this conjugate, standard protocols involve culturing cancer cell lines (e.g., HEK293, HeLa, MM.1S multiple myeloma cells) in appropriate media with 10% FBS at 37degC in 5% CO2. Cells are seeded in 12- or 96-well plates at 1×10⁵ cells per well and allowed to attach overnight. PROTAC is added at concentrations ranging from 0.1 nM to 10 uM for 4-72 hours. Target protein degradation is assessed by western blotting of cell lysates using specific antibodies. CRBN engagement can be confirmed using competition assays with excess thalidomide or lenalidomide (1-10 uM). Cell viability is measured using CellTiter-Glo assays. All experiments are performed in triplicate.
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| Animal Protocol |
For in vivo studies of PROTACs synthesized using Thalidomide-NH-C5-NH2 TFA, standard animal protocols involve xenograft models in immunodeficient mice (nude or NSG mice, 6-8 weeks old, 18-22 g). Approximately 5×10⁶ cancer cells are injected subcutaneously. When tumors reach ~150-200 mm3, mice are randomized into treatment groups (n=5-10 per group). PROTAC is administered intraperitoneally at doses of 1-50 mg/kg in formulation vehicles such as 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline. Tumor volumes are measured every 2-3 days using digital calipers. Body weights are monitored as a toxicity indicator. At study termination, tumors are excised and processed for target protein analysis by western blotting. Blood may be collected for pharmacokinetic analysis.
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| ADME/Pharmacokinetics |
No direct pharmacokinetic studies have been published for Thalidomide-NH-C5-NH2 TFA. Computed properties include the thalidomide-based CRBN ligand with predicted logP of approximately 1.0-1.5. The C5 alkyl linker provides 5 carbon atoms of spacing, with the terminal primary amine enabling conjugation. For PROTACs synthesized using this conjugate, pharmacokinetic parameters such as half-life, clearance, volume of distribution, and bioavailability are determined by the overall molecular properties of the complete PROTAC molecule. Thalidomide-based conjugates are known to have moderate to good oral bioavailability in some cases, but this varies depending on the full PROTAC structure.
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| Toxicity/Toxicokinetics |
Safety data for Thalidomide-NH-C5-NH2 TFA indicates the compound is for research use only. Thalidomide and its derivatives are known teratogens; extreme caution must be exercised when handling this compound to avoid exposure, particularly for women of childbearing potential. Standard laboratory safety precautions should be followed: wear protective gloves, safety goggles, and a lab coat. Work in a well-ventilated fume hood. Avoid inhalation, ingestion, and contact with skin and eyes. The compound should be stored at -20degC, protected from light and moisture. Strict adherence to safety protocols is required. This product is not for human therapeutic use.
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| Additional Infomation |
Thalidomide-NH-C5-NH2 TFA is an E3 ligase ligand-linker conjugate designed for PROTAC (Proteolysis Targeting Chimera) synthesis. This compound features a thalidomide-based cereblon (CRBN) ligand pre-conjugated to a C5 alkyl linker terminating in a primary amine (presented as the TFA salt). The pre-conjugated design simplifies PROTAC assembly by eliminating the need for separate linker conjugation steps. The terminal primary amine serves as a handle for direct amide bond formation with carboxylic acid-containing target protein ligands using standard coupling chemistry. Thalidomide is the prototypical CRBN-binding immunomodulatory drug, and its derivatives are widely used in PROTAC development for targeted protein degradation in cancer research. This product is for research use only and has no approved clinical applications.
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| Molecular Formula |
C20H23F3N4O6
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| Molecular Weight |
472.42
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| CAS # |
2093386-40-2
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| Related CAS # |
Thalidomide-NH-C5-NH2; 2093386-39-9
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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, 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 | 2.1168 mL | 10.5838 mL | 21.1676 mL | |
| 5 mM | 0.4234 mL | 2.1168 mL | 4.2335 mL | |
| 10 mM | 0.2117 mL | 1.0584 mL | 2.1168 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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