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| Targets |
The primary molecular target of Thalidomide-NH-PEG3-NH-Boc is cereblon (CRBN), an E3 ubiquitin ligase substrate receptor. As a ligand for the E3 ubiquitin ligase complex, this compound binds to CRBN and recruits the ubiquitin-proteasome system. In the context of PROTAC technology, the thalidomide moiety serves as the E3 ligase recognition element, while the PEG3 linker provides a spacer for conjugation to a target protein ligand. This bifunctional design enables the targeted degradation of specific proteins by bringing the target protein into proximity with the E3 ligase.
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| ln Vitro |
In vitro studies demonstrate that Thalidomide-NH-PEG3-NH-Boc functions as a key component in PROTAC molecules. The compound contains a thalidomide-based cereblon ligand that binds to the E3 ubiquitin ligase and a PEG3 linker with a Boc-protected amine that can be deprotected and conjugated to a target protein ligand. The PEG3 spacer provides appropriate length and flexibility for the formation of the ternary complex between the target protein, PROTAC, and E3 ligase. This compound is designed to facilitate targeted protein degradation in cellular systems through the ubiquitin-proteasome pathway.
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| ln Vivo |
In vivo activity data for Thalidomide-NH-PEG3-NH-Boc as a standalone compound are not reported, as it is utilized as a synthetic intermediate or linker component in PROTAC design rather than as a therapeutic agent itself. The in vivo efficacy of PROTAC molecules incorporating this thalidomide-based ligand and PEG3 linker would depend on the specific target protein ligand and the overall pharmacokinetic properties of the complete PROTAC construct. As a linker conjugate, its primary role is to facilitate targeted protein degradation through E3 ligase recruitment.
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| Enzyme Assay |
In vitro assays for evaluating Thalidomide-NH-PEG3-NH-Boc typically involve binding studies to assess its interaction with cereblon (CRBN), the E3 ubiquitin ligase substrate receptor. Surface plasmon resonance (SPR) or fluorescence polarization techniques can be used to measure the binding affinity (Kd) between the thalidomide-based ligand and CRBN. Additionally, ternary complex formation assays can be performed to evaluate the ability of PROTAC molecules containing this linker to simultaneously engage both the E3 ligase and the target protein. Competition binding assays using fluorescently labeled probes are also commonly used to determine the inhibitory concentration (IC50) of the ligand for CRBN binding.
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| Cell Assay |
In vitro cell-based assays for Thalidomide-NH-PEG3-NH-Boc typically involve its incorporation into PROTAC molecules followed by evaluation of target protein degradation in cultured cells. Cells are treated with PROTACs containing this thalidomide-based ligand and PEG3 linker, and the levels of the target protein are measured by Western blotting or immunofluorescence to assess degradation efficiency. Dose-response experiments are performed to determine the DC50 (half-maximal degradation concentration) of the PROTAC construct. Additionally, cell viability and proliferation assays may be conducted to evaluate the functional consequences of target protein degradation.
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| Animal Protocol |
In vivo animal studies using Thalidomide-NH-PEG3-NH-Boc are conducted as part of the evaluation of complete PROTAC molecules that incorporate this thalidomide-based ligand and PEG3 linker. Typical protocols involve administering PROTAC constructs to mouse xenograft models or disease-relevant animal models, followed by assessment of target protein degradation in harvested tissues via Western blot or immunohistochemistry. Pharmacodynamic endpoints include measurement of target protein levels, downstream signaling pathway modulation, and tumor growth inhibition in efficacy studies. Dosing regimens are optimized based on the pharmacokinetic properties of the specific PROTAC construct.
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| ADME/Pharmacokinetics |
As a linker conjugate rather than a therapeutic drug, comprehensive pharmacokinetic data for Thalidomide-NH-PEG3-NH-Boc alone are limited. The compound has a molecular formula of C26H36N4O9 and a molecular weight of 548.59. The IUPAC name is tert-butyl (2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)ethyl)carbamate. When incorporated into PROTAC molecules, the thalidomide-based ligand and PEG3 linker contribute to the overall physicochemical properties of the complete construct.
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| Toxicity/Toxicokinetics |
The toxicity profile of Thalidomide-NH-PEG3-NH-Boc as an individual compound is not extensively characterized, as it is primarily used as a research reagent and synthetic intermediate for PROTAC development. The compound is intended for research use only and is not approved for therapeutic use in humans. The thalidomide core structure is known to have teratogenic effects, and appropriate safety precautions should be taken when handling this compound. Standard laboratory safety practices, including the use of personal protective equipment and handling in a fume hood, are recommended.
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| References | |
| Additional Infomation |
Thalidomide-NH-PEG3-NH-Boc (CAS 2204246-03-5) has a molecular formula of C26H36N4O9 and a molecular weight of 548.59. The IUPAC name is tert-butyl N-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]carbamate. It is an advanced E3 ligase ligand-linker conjugate designed for use in targeted protein degradation technologies. The Boc protecting group allows for selective deprotection under acidic conditions. It is part of the E3 ligase ligand-linker conjugate category.
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| Molecular Formula |
C26H36N4O9
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| Molecular Weight |
548.585447311401
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| Exact Mass |
548.248
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| CAS # |
2204246-03-5
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| PubChem CID |
131801484
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| Appearance |
Light yellow to yellow ointment
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
39
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| Complexity |
891
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C(CCC(N1)=O)N1C(C2C=CC=C(C=2C1=O)NCCOCCOCCOCCNC(=O)OC(C)(C)C)=O
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| InChi Key |
ZAQGFFFSCSRSDJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H36N4O9/c1-26(2,3)39-25(35)28-10-12-37-14-16-38-15-13-36-11-9-27-18-6-4-5-17-21(18)24(34)30(23(17)33)19-7-8-20(31)29-22(19)32/h4-6,19,27H,7-16H2,1-3H3,(H,28,35)(H,29,31,32)
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| Chemical Name |
tert-butyl N-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]carbamate
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8229 mL | 9.1143 mL | 18.2285 mL | |
| 5 mM | 0.3646 mL | 1.8229 mL | 3.6457 mL | |
| 10 mM | 0.1823 mL | 0.9114 mL | 1.8229 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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