| Size | Price | |
|---|---|---|
| Other Sizes |
| Targets |
Cereblon
CRBN (cereblon), an E3 ubiquitin ligase. |
|---|---|
| ln Vitro |
As a cereblon-binding ligand, Thalidomide 5-fluoride itself has no intrinsic degradation activity; its function is to bind to cereblon and recruit the E3 ubiquitin ligase complex. When conjugated to an IRAK4-binding ligand via an appropriate linker, the resulting PROTAC IRAK4 degrader-1 can simultaneously bind to both IRAK4 and cereblon, leading to ubiquitination and subsequent proteasomal degradation of IRAK4. The fluorine atom at the 5-position may enhance the binding affinity to cereblon and improve the metabolic stability of the ligand compared to Thalidomide. This compound is a key component of PROTAC IRAK4 degrader-1, which has been developed for the treatment of IRAK4-driven inflammatory diseases and cancers.
|
| ln Vivo |
No specific in vivo activity has been reported for this ligand alone; its in vivo degradation activity is observed only when conjugated to an IRAK4 ligand to form the complete PROTAC IRAK4 degrader-1 molecule. The in vivo efficacy of this PROTAC is being evaluated in animal models of IRAK4-driven diseases.
|
| Enzyme Assay |
N/A; as a ligand, its binding affinity to cereblon is typically determined using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) as part of the validation of the final PROTAC construct. The compound is used as a synthetic intermediate. The purity of the compound is typically confirmed by HPLC, with a standard purity of ≥95-98%. The fluorine atom can be characterized by 19F NMR spectroscopy.
|
| Cell Assay |
N/A; this ligand is not evaluated alone in cell-based assays but is used as a building block to construct cereblon-recruiting PROTACs. In the synthesis of PROTAC IRAK4 degrader-1, the thalidomide 5-fluoride ligand is conjugated to an IRAK4-binding ligand via a linker using standard coupling chemistry. The resulting PROTAC is then tested in IRAK4-expressing cells for degradation activity by Western blotting to determine the DC50 (half-maximal degradation concentration). PROTAC IRAK4 degrader-1 has been reported to degrade IRAK4 in cells with high potency.
|
| Animal Protocol |
N/A; no animal studies are performed with the ligand alone. In vivo efficacy studies for PROTAC IRAK4 degrader-1 would be conducted in mouse xenograft models of IRAK4-driven cancers or in models of inflammatory disease. The complete PROTAC would be formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered via intraperitoneal (IP) or intravenous (IV) injection. Target degradation in tissues and disease progression (tumor growth or inflammation) would be monitored.
|
| ADME/Pharmacokinetics |
This compound has a molecular weight of 276.22, a molecular formula of C13H9FN2O4, and a standard purity of ≥95-98%. The IUPAC name is 2-(2,6-dioxopiperidin-3-yl)-5-fluoro-2,3-dihydro-1H-isoindole-1,3-dione. For storage, it should be kept as a solid at -20degC for up to 3 years, sealed, away from moisture. It is soluble in DMSO. The product should be stored under nitrogen to avoid moisture absorption. CAS: 835616-61-0.
|
| Toxicity/Toxicokinetics |
This product is for research use only and is not for human or veterinary use. Standard chemical safety precautions should be observed during handling. Thalidomide is an immunomodulatory drug with known teratogenic effects; this derivative is for research purposes only and should be handled with appropriate caution. It is not an approved therapeutic drug and has not been cleared for clinical use. PROTAC is a registered trademark of Arvinas Operations, Inc., and is used under license.
|
| References | |
| Additional Infomation |
The fluorine atom at the 5-position of the isoindole ring is a modification that can enhance the binding affinity and metabolic stability of the thalidomide-based cereblon ligand. This modification is part of the structure of PROTAC IRAK4 degrader-1, a research compound that targets IRAK4, an interleukin-1 receptor-associated kinase involved in innate immune signaling. IRAK4 is a promising therapeutic target for inflammatory diseases such as rheumatoid arthritis, as well as for certain hematologic malignancies. Thalidomide 5-fluoride enables the construction of potent and selective IRAK4-degrading PROTACs and is a valuable building block for studying IRAK4 biology and developing novel therapeutics.
|
| Molecular Formula |
C13H9FN2O4
|
|---|---|
| Molecular Weight |
276.22
|
| Exact Mass |
276.055
|
| CAS # |
835616-61-0
|
| Related CAS # |
Thalidomide 4-fluoride;835616-60-9
|
| PubChem CID |
70876201
|
| Appearance |
Off-white to gray solid powder
|
| Density |
1.570±0.06 g/cm3
|
| Boiling Point |
521.5±45.0 °C at 760 mmHg
|
| LogP |
0.44
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
20
|
| Complexity |
507
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1N(C2CCC(=O)NC2=O)C(=O)C2C1=CC=C(C=2)F
|
| InChi Key |
MPQLCQKBYRSPNA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C13H9FN2O4/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,3-4H2,(H,15,17,18)
|
| Chemical Name |
2-(2,6-dioxopiperidin-3-yl)-5-fluoroisoindole-1,3-dione
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO :~50 mg/mL (~181.02 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6203 mL | 18.1015 mL | 36.2030 mL | |
| 5 mM | 0.7241 mL | 3.6203 mL | 7.2406 mL | |
| 10 mM | 0.3620 mL | 1.8102 mL | 3.6203 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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