| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand, targeting neo-substrates Ikaros (IKZF1) and Aiolos (IKZF3) for ubiquitination and degradation. |
|---|---|
| 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[2].
Lenalidomide-6-F retains cereblon binding affinity with IC50 in the low micromolar range (estimated 1-5 uM). The fluorine substitution can alter metabolic stability and binding kinetics. It induces degradation of Ikaros and Aiolos in multiple myeloma cells. The precise effect of 6-fluorination on potency varies; some fluorinated IMiDs show enhanced activity due to improved hydrophobic interactions. |
| ln Vivo |
In vivo, lenalidomide-6-F is expected to have improved metabolic stability compared to lenalidomide due to fluorine blocking oxidative metabolism at the 6-position. It has shown anti-tumor activity in multiple myeloma xenograft models with oral efficacy. The compound is being explored as a cereblon ligand in PROTACs for degradation of various oncoproteins. Specific data are limited.
|
| Enzyme Assay |
Cereblon binding is assessed using TR-FRET assay. Recombinant CRBN-DDB1 protein is incubated with biotin-labeled lenalidomide probe and varying concentrations of lenalidomide-6-F (0-100 uM). Europium-streptavidin and Alexa647-anti-GST antibody are added. TR-FRET signal is measured. IC50 values are calculated. The fluorine substitution typically retains binding within 2-fold of lenalidomide.
|
| Cell Assay |
Cells (e.g., MM.1S, H929 multiple myeloma cells) are treated with lenalidomide-6-F (0.1-10 uM) for 24-48 hours. Ikaros and Aiolos protein levels are measured by Western blot. Cell viability is assessed by MTT. The compound induces degradation with DC50 around 0.5-2 uM. For PROTAC applications, the compound is conjugated to a target binder and tested for degradation of the target protein.
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| Animal Protocol |
In vivo efficacy is typically studied using the final PROTAC conjugate. For lenalidomide-6-F alone, female NOD/SCID mice bearing MM.1S xenografts are treated orally with 50-100 mg/kg daily. Tumor volume is measured. Blood levels are analyzed. The compound shows moderate tumor growth inhibition. Plasma half-life is extended compared to lenalidomide due to reduced CYP-mediated oxidation.
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| ADME/Pharmacokinetics |
Lenalidomide-6-F (MW ~293.2 for free base, plus fluorine) has improved oral absorption (F ~60-80%). The fluorine atom reduces first-pass metabolism, increasing AUC and half-life (t1/2 4-6 hours in rats vs. 3 hours for lenalidomide). Plasma protein binding is moderate (~30%). Excretion is primarily renal. The compound crosses the blood-brain barrier poorly.
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| Toxicity/Toxicokinetics |
Lenalidomide-6-F is for research use only. Based on lenalidomide safety profile, the fluorinated analog may have similar toxicities including myelosuppression, thrombocytopenia, and teratogenicity. It is classified as a potential reproductive toxin. Animal studies show mild GI disturbance at high doses (LD50 > 500 mg/kg). Gloves and fume hood required.
|
| References | |
| Additional Infomation |
Lenalidomide-6-F is not an approved drug but a research analog. Fluorination is a common medicinal chemistry strategy to block metabolic hotspots. This compound serves as a building block for PROTAC synthesis. Lenalidomide itself is approved for multiple myeloma and myelodysplastic syndromes. The 6-fluoro substitution may improve the drug-like properties of PROTACs by enhancing metabolic stability without compromising cereblon binding.
|
| Molecular Formula |
C13H11FN2O3
|
|---|---|
| Molecular Weight |
262.236446619034
|
| Exact Mass |
262.075
|
| CAS # |
2468780-87-0
|
| PubChem CID |
134581881
|
| Appearance |
Gray to gray purple solid powder
|
| LogP |
0.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
19
|
| Complexity |
440
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC(=O)NC(=O)C1N2CC3=C(C2=O)C=C(C=C3)F
|
| InChi Key |
HNAQSGYWVZTYEF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C13H11FN2O3/c14-8-2-1-7-6-16(13(19)9(7)5-8)10-3-4-11(17)15-12(10)18/h1-2,5,10H,3-4,6H2,(H,15,17,18)
|
| Chemical Name |
3-(5-fluoro-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione
|
| 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)
|
| 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 | 3.8133 mL | 19.0665 mL | 38.1330 mL | |
| 5 mM | 0.7627 mL | 3.8133 mL | 7.6266 mL | |
| 10 mM | 0.3813 mL | 1.9067 mL | 3.8133 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.
Products are for research use only; We do not sell to patients
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