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| Other Sizes |
| Targets |
Cereblon (CRBN); E3 ubiquitin ligase complex. 5-Aminothalidomide is a cereblon (CRBN) ligand used in PROTAC technology. By binding to CRBN, it recruits the E3 ubiquitin ligase complex to target proteins for ubiquitination and subsequent proteasomal degradation. It is a functionalized ligand with an amine group for conjugation to target-binding moieties.
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| ln Vitro |
5-Aminothalidomide inhibits lipopolysaccharide-stimulated TNF-alpha release in human PBMC with an inhibition rate of 55.0% at 100 µM and an IC₅₀ of 100,000 nM in human whole blood. It displaces fluorescent tracer from NanoLuc-tagged CRBN with an IC₅₀ of 560 nM in the NanoBRET assay. It induces IKZF1 degradation in human MOLT-4 cells with a maximum degradation of 38.0% after 24 hours. It also inhibits proliferation of EA.hy926 endothelial cells (IC₅₀ = 200 µM).
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| ln Vivo |
In vivo studies of 5-aminothalidomide are limited to its use as an intermediate in PROTAC synthesis. PROTACs incorporating 5-aminothalidomide as the E3 ligase ligand have shown antiproliferative activity in c-MET-sensitive cancer cells. The compound itself is not the active therapeutic agent but serves as a building block for targeted protein degraders.
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| Enzyme Assay |
Non-cell-based assays for 5-aminothalidomide include CRBN binding assays such as NanoBRET to assess displacement of fluorescent tracer from NanoLuc-tagged CRBN. The compound's ability to function as an E3 ligase ligand is confirmed through binding studies. Standard analytical methods including HPLC, NMR, and mass spectrometry are used for compound characterization and purity assessment.
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| Cell Assay |
Cell-based assays for 5-aminothalidomide use human PBMC to assess TNF-alpha release inhibition. MOLT-4 cells are used to assess IKZF1 degradation. EA.hy926 endothelial cells are used to assess proliferation inhibition (IC₅₀ = 200 µM). PROTAC molecules incorporating 5-aminothalidomide are tested in cancer cell lines for antiproliferative activity. Cytotoxicity is assessed using standard cell viability assays.
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| Animal Protocol |
In vivo studies of PROTAC molecules incorporating 5-aminothalidomide are conducted in mouse xenograft models of c-MET-sensitive cancers. The PROTAC is administered via intraperitoneal or intravenous injection. Tumor volume is measured over time to assess antitumor efficacy. Pharmacokinetic parameters are determined from blood samples. The 5-aminothalidomide moiety serves as the E3 ligase-recruiting component of the PROTAC.
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| ADME/Pharmacokinetics |
5-Aminothalidomide has a molecular formula of C₁₃H₁₁N₃O₄ and a molecular weight of 273.24 g/mol. Purity is ≥95%. It is a solid with a green color. Storage: powder at -20°C for 3 years; in solvent at -80°C for 1 year. It is soluble in DMSO and acetonitrile. It is a derivative of (±)-thalidomide.
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| Toxicity/Toxicokinetics |
5-Aminothalidomide is a derivative of the immunomodulatory compound (±)-thalidomide. It inhibits proliferation of EA.hy926 endothelial cells (IC₅₀ = 200 µM). It is an intermediate in the synthesis of PROTAC c-MET degraders with antiproliferative activity in c-MET-sensitive cancer cells. Standard laboratory safety practices should be followed when handling this compound. It is intended for research use only.
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| References | |
| Additional Infomation |
5-Aminothalidomide is a functionalized cereblon (CRBN) ligand for PROTAC research and development. It incorporates an E3 ligase ligand with an amine on the C5 position of the phthalimide ring for onward chemistry to generate protein degraders. It is a derivative of (±)-thalidomide. It inhibits proliferation of EA.hy926 endothelial cells (IC₅₀ = 200 µM) and is an intermediate in the synthesis of PROTAC c-MET degraders. It is for research use only.
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| Molecular Formula |
C13H11N3O4
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|---|---|
| Molecular Weight |
273.24
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| Exact Mass |
273.075
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| CAS # |
191732-76-0
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| PubChem CID |
9816958
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| Appearance |
Light yellow to green yellow solid powder
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| Density |
1.570±0.06 g/cm3(Predicted)
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| Boiling Point |
603.8±50.0 °C(Predicted)
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| Melting Point |
322 °C
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| LogP |
0.465
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
20
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| Complexity |
504
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C([H])(C([H])([H])C([H])([H])C(N1[H])=O)N1C(C2C([H])=C([H])C(=C([H])C=2C1=O)N([H])[H])=O
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| InChi Key |
IICWMVJMJVXCLY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H11N3O4/c14-6-1-2-7-8(5-6)13(20)16(12(7)19)9-3-4-10(17)15-11(9)18/h1-2,5,9H,3-4,14H2,(H,15,17,18)
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| Chemical Name |
5-amino-2-(2,6-dioxopiperidin-3-yl)isoindole-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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO: ~50 mg/mL (~183.0 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.15 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6598 mL | 18.2989 mL | 36.5979 mL | |
| 5 mM | 0.7320 mL | 3.6598 mL | 7.3196 mL | |
| 10 mM | 0.3660 mL | 1.8299 mL | 3.6598 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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