| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Targets |
Target: Cereblon (CRBN), a substrate receptor of the CRL4 E3 ubiquitin ligase complex. Lenalidomide binds to cereblon, altering the substrate specificity of the CRL4CRBN E3 ubiquitin ligase, leading to selective ubiquitination and degradation of the lymphoid transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos). This results in immunomodulatory and anti-neoplastic effects. The deuterated standard is an analytical tracer.
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|---|---|
| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
In vitro, the labeled standard has no direct biological activity. The unlabeled lenalidomide (0.1 nM to 10 uM) induces ubiquitination and degradation of IKZF1 and IKZF3 in multiple myeloma cells (e.g., MM.1S, H929) and other hematologic cancer cells, leading to cell cycle arrest and apoptosis. It also increases T cell and NK cell activation, enhances antibody-dependent cellular cytotoxicity (ADCC), and inhibits angiogenesis by reducing VEGF production. |
| ln Vivo |
In vivo, the unlabeled lenalidomide is orally active and has demonstrated significant antitumor efficacy in xenograft models of multiple myeloma, non-Hodgkin lymphoma (NHL), and myelodysplastic syndromes (MDS). It reduces tumor burden, prolongs survival, and induces durable remissions in patients with relapsed/refractory multiple myeloma and MDS with deletion 5q. The deuterated standard is not administered in vivo but is used to quantify lenalidomide in PK studies.
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| Enzyme Assay |
For cell-free assays (LC-MS/MS): plasma, serum, or urine samples are spiked with Lenalidomide-d5 internal standard. After protein precipitation with acetonitrile or methanol, and centrifugation, the supernatant is injected into an LC-MS/MS system. A C18 reverse-phase column and positive ion mode ESI-MS/MS are typically used. Quantitation is based on the analyte/internal standard peak area ratio. Isotope dilution mass spectrometry is used to correct for matrix effects and ensure accurate quantification of lenalidomide and its metabolites.
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| Cell Assay |
For cell-based assays: multiple myeloma cells (e.g., MM.1S, H929, OPM2) or other hematologic cancer cells are seeded in 96-well plates and treated with lenalidomide (0.001-10 uM, 48-96 h). Cell viability is measured by MTT or CellTiter-Glo assay. Apoptosis is assessed by Annexin V/PI flow cytometry. IKZF1 and IKZF3 degradation is confirmed by Western blot. The deuterated standard is not used in these assays; it is used for LC-MS quantification of lenalidomide concentrations in cell culture media for uptake and metabolism studies.
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| Animal Protocol |
For animal studies (PK/PD studies): immunodeficient mice (e.g., NSG, SCID) bearing multiple myeloma xenografts (e.g., MM.1S, H929) are administered lenalidomide orally (5-50 mg/kg) daily for 2-4 weeks. Serial blood samples are collected for PK analysis using Lenalidomide-d5 internal standard in LC-MS/MS. Tumor volumes are measured by calipers, and tumor tissues are harvested for Western blot analysis of IKZF1/IKZF3 degradation and apoptosis markers. The labeled standard is used in bioanalysis but is not administered to animals directly.
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| ADME/Pharmacokinetics |
PK properties of lenalidomide: after oral administration, it is rapidly absorbed (Tmax 0.5-2 h) with high oral bioavailability (>90%). Plasma protein binding is low (~30%). It is minimally metabolized (primarily by CYP1A2 and CYP2D6, with <50% of the dose metabolized). Approximately 80-85% of the dose is excreted unchanged in urine. The terminal elimination half-life is approximately 3-5 h. No significant accumulation occurs with repeated dosing. The deuterated standard co-elutes with the analyte, ensuring accurate PK parameter determination by stable isotope dilution LC-MS/MS.
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| Toxicity/Toxicokinetics |
Toxicity profile of lenalidomide (unlabeled): Common adverse effects include neutropenia, thrombocytopenia, anemia, fatigue, diarrhea, constipation, nausea, rash, and muscle cramps. Serious adverse effects include deep vein thrombosis (DVT), pulmonary embolism (PE), increased risk of second primary malignancies (e.g., AML, MDS), hepatotoxicity, and severe cutaneous reactions (Stevens-Johnson syndrome, TEN). Lenalidomide is teratogenic and is only available under a restricted distribution program (REMS). The labeled compound is for research use only and is not intended for human administration.
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| References | |
| Additional Infomation |
Lenalidomide-d5 is a research standard and not an active drug substance. The unlabeled lenalidomide (Revlimid) is FDA-approved for the treatment of multiple myeloma (MM), myelodysplastic syndromes (MDS) with deletion 5q, mantle cell lymphoma (MCL), and follicular lymphoma (FL). It is a cornerstone of MM therapy, often used in combination with dexamethasone, bortezomib, or daratumumab. The deuterated standard is used for analytical method development, method validation (AMV), quality control (QC), and abbreviated new drug application (ANDA) submissions for lenalidomide-containing pharmaceutical products. It is essential for therapeutic drug monitoring (TDM) and clinical PK studies.
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| Molecular Formula |
C13H13N3O3
|
|---|---|
| Molecular Weight |
259.260622739792
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| Exact Mass |
264.127
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| CAS # |
1227162-34-6
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| Related CAS # |
Lenalidomide;191732-72-6;Lenalidomide sodium
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| PubChem CID |
46208619
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
614.0±55.0 °C at 760 mmHg
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| Flash Point |
325.1±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.672
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| LogP |
-1.39
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
437
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1(C(=O)NC(=O)C(C1([2H])[2H])([2H])N2CC3=C(C2=O)C=CC=C3N)[2H]
|
| InChi Key |
GOTYRUGSSMKFNF-QTQWIGFBSA-N
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| InChi Code |
InChI=1S/C13H13N3O3/c14-9-3-1-2-7-8(9)6-16(13(7)19)10-4-5-11(17)15-12(10)18/h1-3,10H,4-6,14H2,(H,15,17,18)/i4D2,5D2,10D
|
| Chemical Name |
3-(7-amino-3-oxo-1H-isoindol-2-yl)-3,4,4,5,5-pentadeuteriopiperidine-2,6-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 | 3.8571 mL | 19.2857 mL | 38.5713 mL | |
| 5 mM | 0.7714 mL | 3.8571 mL | 7.7143 mL | |
| 10 mM | 0.3857 mL | 1.9286 mL | 3.8571 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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