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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
The compound targets cereblon (CRBN), a component of the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex. The thalidomide-based ligand binds to CRBN, recruiting the E3 ligase machinery. When conjugated to a target protein ligand, the resulting PROTAC molecule brings the target protein into proximity with the E3 ligase, leading to target ubiquitination and subsequent proteasomal degradation. The C8 alkyl linker (8 carbons) is fully hydrophobic, offering a different physicochemical property profile compared to hydrophilic PEG-based linkers, which may be advantageous for specific target protein configurations requiring minimal hydrophilic character.
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| ln Vitro |
In vitro activity of this compound is realized through its use as a PROTAC building block. When conjugated to a target protein-binding ligand, the resulting PROTAC induces target protein ubiquitination and proteasome-dependent degradation. The ligand-linker conjugate alone exhibits minimal intrinsic biological activity. In cell-based assays, PROTACs constructed with C8 alkyl linkers have been evaluated for degradation of various target proteins. Standard validation involves treating cells with the PROTAC at concentrations ranging from 0.001-10 uM for 4-24 hours, followed by Western blot analysis to quantify target protein levels. The shorter C8 linker may be optimal for target proteins where the distance between CRBN and the target binding site is minimal.
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| ln Vivo |
In vivo efficacy studies with PROTACs incorporating the C8 linker are typically conducted in murine xenograft models. Complete PROTAC molecules are administered to tumor-bearing immunodeficient mice via intraperitoneal (IP) or intravenous (IV) routes at doses ranging from 1-30 mg/kg. Dosing frequency is typically daily or every other day for 2-4 weeks. The hydrophobic C8 alkyl linker reduces aqueous solubility compared to PEG-based linkers, often requiring formulation with co-solvents such as DMSO, PEG300, Tween 80, or cyclodextrins for adequate solubility. Efficacy is assessed by tumor volume measurements, Western blot analysis of target protein degradation in harvested tumor tissues, and evaluation of pharmacodynamic biomarkers.
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| Enzyme Assay |
CRBN-binding affinity of the thalidomide-5-O component can be measured using fluorescence polarization (FP) or surface plasmon resonance (SPR). For FP competitive binding assays, purified CRBN-DDB1 complex is incubated with a fluorescently labeled thalidomide probe and varying concentrations of the test compound. Binding (IC50) is determined by measuring displacement of the probe. Typical assay conditions: 50 mM HEPES (pH 7.4), 150 mM NaCl, 1 mM DTT, 0.01% Tween-20, 0.1 mg/mL BSA. The C8 linker attached at the 5-O position is known to not interfere with CRBN binding, as this position is a standard attachment point in PROTAC design. Thalidomide-based CRBN ligands typically exhibit KD values in the low micromolar range (approximately 1-10 uM).
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| Cell Assay |
To construct a PROTAC molecule using this building block, the terminal primary amine is conjugated to a target protein ligand containing a carboxylic acid via standard amide coupling. Typical procedure: The target ligand carboxylic acid (1.0 equiv) is dissolved in anhydrous DMF or DMSO with HATU (1.2 equiv) and DIPEA (2-3 equiv) and activated for 10-30 minutes at room temperature. The amine linker (1.0-1.2 equiv) is added, and the reaction is stirred for 2-12 hours. The resulting PROTAC is purified by preparative HPLC and characterized by LC-MS. For cellular activity validation, cells are treated with the PROTAC (0.001-10 uM, 4-24 h), then lysed and analyzed by Western blotting to assess target protein degradation. Control treatments include the unconjugated target ligand alone and the CRBN ligand alone.
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| Animal Protocol |
In vivo animal studies with PROTACs containing the C8 linker follow standard xenograft protocols. Immunodeficient mice (nude or NSG, 6-8 weeks old, n=5-10 per group) bearing subcutaneous human tumor xenografts are randomized into treatment groups when tumors reach approximately 100-200 mm3. PROTACs are formulated in a vehicle appropriate for hydrophobic compounds (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline; or 10% DMSO, 90% corn oil) and administered IP or IV at 1-30 mg/kg. Dosing frequency ranges from once daily to three times weekly. Tumor volumes (calculated as 0.5 × length × width2) and body weights are recorded every 2-3 days. At study termination (typically 2-4 weeks), tumors are harvested for Western blot or IHC analysis of target protein degradation, and plasma is collected for PK analysis.
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| ADME/Pharmacokinetics |
For the standalone ligand-linker conjugate, the C8 alkyl linker (8 carbons) contributes significantly to the overall lipophilicity. When incorporated into PROTACs, the hydrophobic C8 linker may affect pharmacokinetic properties including reduced aqueous solubility (often <1 mg/mL in simple aqueous buffers), increased plasma protein binding (which may prolong half-life but reduce free drug concentration), and potentially improved cell permeability compared to highly hydrophilic linkers. However, high lipophilicity also increases risk of off-target binding and non-specific toxicity. The hydrochloride salt form improves water solubility for handling and storage, though further formulation is typically required for in vivo administration. No dedicated PK studies are available for the ligand-linker conjugate alone.
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| Toxicity/Toxicokinetics |
Toxicology data specific to Thalidomide-5-O-C8-NH2 hydrochloride is not publicly available. As a thalidomide-derived compound, it shares the core cereblon-binding structure responsible for the teratogenic effects of thalidomide. The C8 alkyl linker and hydrochloride salt do not eliminate this potential toxicity. Therefore, strict handling precautions are required: work in a chemical fume hood, use appropriate PPE (gloves, lab coat, safety glasses), avoid inhalation, skin contact, and ingestion. Pregnant or potentially pregnant individuals should avoid handling thalidomide-derived compounds. This product is for research use only; not for human use, therapeutic applications, or diagnostic purposes.
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| Additional Infomation |
Thalidomide-5-O-C8-NH2 hydrochloride is a research tool for PROTAC-based targeted protein degradation studies. The compound is part of a series of alkyl linker variants (C7 through C14) allowing systematic optimization of linker length for specific target proteins. The C8 linker provides a shorter spacer compared to C9-C14 variants, which may be optimal for target proteins where the distance between CRBN and the target binding site is minimal. This compound is strictly for laboratory research applications including chemical biology, cancer research, and drug discovery. It has not been evaluated in clinical trials and is not an approved drug. Storage: powder at -20degC, protected from light and moisture, under inert atmosphere.
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| Molecular Formula |
C21H28CLN3O5
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| Molecular Weight |
437.92
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| Appearance |
White to off-white 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 | 2.2835 mL | 11.4176 mL | 22.8352 mL | |
| 5 mM | 0.4567 mL | 2.2835 mL | 4.5670 mL | |
| 10 mM | 0.2284 mL | 1.1418 mL | 2.2835 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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