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| 1mg |
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| Other Sizes |
| Targets |
The primary molecular target of Thalidomide-5-methyl 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 methyl group at the 5-position may modulate binding affinity and physicochemical properties.
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| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[1].
In vitro studies demonstrate that Thalidomide-5-methyl functions as a cereblon ligand in PROTAC molecules. The compound binds to the E3 ubiquitin ligase via the CRBN protein. The methyl group at the 5-position may influence the binding affinity and selectivity for CRBN. This compound is designed to facilitate targeted protein degradation in cellular systems through the ubiquitin-proteasome pathway. It is typically used as a synthetic building block in the preparation of complete PROTAC molecules. |
| ln Vivo |
In vivo activity data for Thalidomide-5-methyl as a standalone compound are not reported, as it is utilized as a synthetic building block or ligand in PROTAC design rather than as a therapeutic agent itself. The in vivo efficacy of PROTAC molecules incorporating this thalidomide-based ligand would depend on the specific target protein ligand and the overall pharmacokinetic properties of the complete PROTAC construct.
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| Enzyme Assay |
In vitro assays for evaluating Thalidomide-5-methyl 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. 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-5-methyl 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 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.
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| Animal Protocol |
In vivo animal studies using Thalidomide-5-methyl are conducted as part of the evaluation of complete PROTAC molecules that incorporate this thalidomide-based ligand. 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 and downstream signaling pathway modulation.
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| ADME/Pharmacokinetics |
As a ligand building block rather than a therapeutic drug, comprehensive pharmacokinetic data for Thalidomide-5-methyl alone are limited. The compound has a molecular formula of C14H12N2O4 and a molecular weight of 272.26. The predicted density is 1.448 g/cm³. It has a purity of ≥98%. The IUPAC name is 2-(2,6-dioxopiperidin-3-yl)-5-methylisoindoline-1,3-dione.
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| Toxicity/Toxicokinetics |
The toxicity profile of Thalidomide-5-methyl as an individual compound is not extensively characterized, as it is primarily used as a research reagent and synthetic building block 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.
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| References | |
| Additional Infomation |
Thalidomide-5-methyl (CAS 40313-92-6) has a molecular formula of C14H12N2O4 and a molecular weight of 272.26. It is a Thalidomide-based cereblon (CRBN) ligand used for the recruitment of CRBN protein. The compound features a methyl group at the 5-position of the isoindoline ring. It is part of the E3 ligase ligand building block category for PROTAC synthesis.
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| Molecular Formula |
C14H12N2O4
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| Molecular Weight |
272.256
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| Exact Mass |
272.079
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| CAS # |
40313-92-6
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| PubChem CID |
21847923
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| Appearance |
Gray to gray purple solid powder
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| LogP |
0.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
20
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| Complexity |
501
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C(N2C(=O)C3C(=CC=C(C)C=3)C2=O)CCC(=O)N1
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| InChi Key |
FIRKPGPRAMCBHV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H12N2O4/c1-7-2-3-8-9(6-7)14(20)16(13(8)19)10-4-5-11(17)15-12(10)18/h2-3,6,10H,4-5H2,1H3,(H,15,17,18)
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| Chemical Name |
2-(2,6-dioxopiperidin-3-yl)-5-methylisoindole-1,3-dione
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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 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 | 3.6730 mL | 18.3648 mL | 36.7296 mL | |
| 5 mM | 0.7346 mL | 3.6730 mL | 7.3459 mL | |
| 10 mM | 0.3673 mL | 1.8365 mL | 3.6730 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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