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  2. Ligands for E3 Ligase Molecular Glues Apoptosis
  3. Lenalidomide

Lenalidomide  (Synonyms: CC-5013)

Cat. No.: HY-A0003 Purity: 99.95%
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Lenalidomide (CC-5013), a derivative of Thalidomide, acts as molecular glue. Lenalidomide is an orally active immunomodulator. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide (CC-5013) specifically inhibits growth of mature B-cell lymphomas, including multiple myeloma, and induces IL-2 release from T cells.

For research use only. We do not sell to patients.

Lenalidomide Chemical Structure

Lenalidomide Chemical Structure

CAS No. : 191732-72-6

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Customer Review

Based on 43 publication(s) in Google Scholar

Other Forms of Lenalidomide:

Top Publications Citing Use of Products

39 Publications Citing Use of MCE Lenalidomide

WB

    Lenalidomide purchased from MedChemExpress. Usage Cited in: Cell. 2018 Sep 20;175(1):171-185.e25.  [Abstract]

    WB analysis of MV4-11 cells treated for 6.5 hr with Lenalidomide, BTX161, A51, or A86 at the indicated concentrations or DMSO.

    Lenalidomide purchased from MedChemExpress. Usage Cited in: Elife. 2018 Aug 1;7:e38430.  [Abstract]

    H9 hESC are treated with increasing concentrations of Thalidomide, Lenalidomide, Pomalidomide, or DMSO as a control. Following 24 h of incubation, SALL4 and GAPDH protein levels are assessed by western blot analysis.

    Lenalidomide purchased from MedChemExpress. Usage Cited in: Oncol Rep. 2018 Jun;39(6):2873-2880.  [Abstract]

    Representative western blot membranes showing the expression levels of NF-κB p-p65 and H3 in nuclear protein and of NF-κB p65 and β-actin in total protein. β-actin and H3 are used as internal controls.

    Lenalidomide purchased from MedChemExpress. Usage Cited in: Nat Commun. 2017 May 22;8:15398.  [Abstract]

    HEK293T cells are treated with 50 μg/mL Cycloheximide and increasing concentrations of Lenalidomide, Thalidomide or with DMSO, and cells are incubated for 6 h. ZFP91 and GAPDH levels are detected using anti-ZFP91 or anti-GAPDH immunoblotting.

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    • References

    • Customer Review

    Description

    Lenalidomide (CC-5013), a derivative of Thalidomide, acts as molecular glue. Lenalidomide is an orally active immunomodulator. Lenalidomide (CC-5013) is a ligand of ubiquitin E3 ligase cereblon (CRBN), and it causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase. Lenalidomide (CC-5013) specifically inhibits growth of mature B-cell lymphomas, including multiple myeloma, and induces IL-2 release from T cells[1][2].

    IC50 & Target[5]

    Cereblon

     

    Cellular Effect
    Cell Line Type Value Description References
    EC9706 IC50
    340.3 μg/mL
    Compound: Lenalidomide
    Antiproliferative activity against human EC9706 cells after 48 hrs by CCK-8 assay
    Antiproliferative activity against human EC9706 cells after 48 hrs by CCK-8 assay
    [PMID: 28757066]
    HCC827 IC50
    > 10 μM
    Compound: Lenalidomide
    Antiproliferative activity against human HCC827 cells harboring EGFRDel19 mutant assessed as reduction in cell viability incubated for 72 hrs by MTT assay
    Antiproliferative activity against human HCC827 cells harboring EGFRDel19 mutant assessed as reduction in cell viability incubated for 72 hrs by MTT assay
    [PMID: 31951960]
    HEK293 IC50
    5.19 μM
    Compound: Lenalidomide
    Inhibition of BRD4 bromodomain 2 (unknown origin) in HEK293 cells cotransfected with eGFP by flow cytometry based mCherry reporter gene analysis
    Inhibition of BRD4 bromodomain 2 (unknown origin) in HEK293 cells cotransfected with eGFP by flow cytometry based mCherry reporter gene analysis
    [PMID: 32550984]
    JeKo-1 IC50
    > 20000 nM
    Compound: Lenalidomide
    Antiproliferative activity against human Jeko-1 cells assessed as cell viability measured after 7 days by CCK-8 assay
    Antiproliferative activity against human Jeko-1 cells assessed as cell viability measured after 7 days by CCK-8 assay
    [PMID: 35635954]
    JeKo-1 IC50
    > 20000 nM
    Compound: Lenalidomide
    Antiproliferative activity against human Jeko-1 cells expressing CRBN-knockout assessed as cell viability measured after 7 days by CCK-8 assay
    Antiproliferative activity against human Jeko-1 cells expressing CRBN-knockout assessed as cell viability measured after 7 days by CCK-8 assay
    [PMID: 35635954]
    JeKo-1 IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human JeKo1 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human JeKo1 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    K562 IC50
    > 10 μM
    Compound: Lenalidomide
    Antiproliferative activity against human K562 cells assessed as inhibition of cell growth incubated for 2 days by CCK8 assay
    Antiproliferative activity against human K562 cells assessed as inhibition of cell growth incubated for 2 days by CCK8 assay
    [PMID: 36306539]
    K562 IC50
    > 10 μM
    Compound: Lenalidomide
    Antiproliferative activity against human K562 cells assessed as cell growth inhibition measured after 48 hrs by CCK8 assay
    Antiproliferative activity against human K562 cells assessed as cell growth inhibition measured after 48 hrs by CCK8 assay
    [PMID: 34217059]
    Kasumi 1 IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human Kasumi-1 cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human Kasumi-1 cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    MCF-10A IC50
    > 20 μM
    Compound: Lenalidomide
    Cytotoxicity against human MCF10A cells after 72 hrs by MTS assay
    Cytotoxicity against human MCF10A cells after 72 hrs by MTS assay
    [PMID: 29795767]
    MM1.S IC50
    > 20000 nM
    Compound: Lenalidomide
    Antiproliferative activity against human MM1.S cells assessed as cell viability measured after 3 days by CCK-8 assay
    Antiproliferative activity against human MM1.S cells assessed as cell viability measured after 3 days by CCK-8 assay
    [PMID: 35635954]
    MM1.S IC50
    0.081 μM
    Compound: Lenalidoamide
    Antiproliferative activity against human MM1.S cells assessed as reduction in cell growth measured after 7 days culturing by CellTiter 96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human MM1.S cells assessed as reduction in cell growth measured after 7 days culturing by CellTiter 96 Aqueous non-radioactive cell proliferation assay
    [PMID: 33328101]
    MM1.S IC50
    50 nM
    Compound: 1
    Antiproliferative activity against human MM1S cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human MM1S cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    MM1.S IC50
    70.17 nM
    Compound: Lenalidomide
    Antiproliferative activity against human MM1.S cells assessed as cell viability measured after 7 days by CCK-8 assay
    Antiproliferative activity against human MM1.S cells assessed as cell viability measured after 7 days by CCK-8 assay
    [PMID: 35635954]
    MV4-11 IC50
    > 20000 nM
    Compound: Lenalidomide
    Antiproliferative activity against human MV411 cells after 72 hrs by MTS assay
    Antiproliferative activity against human MV411 cells after 72 hrs by MTS assay
    [PMID: 29795767]
    MV4-11 IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human MV411 cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human MV411 cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    NAMALVA IC50
    0.36 μM
    Compound: 1
    Antiproliferative activity against human NAMALWA cells assessed as inhibition of [3H]thymidine incorporation after 72 hrs by scintillation counting
    Antiproliferative activity against human NAMALWA cells assessed as inhibition of [3H]thymidine incorporation after 72 hrs by scintillation counting
    [PMID: 23168019]
    PBMC IC50
    > 20000 nM
    Compound: 1
    Cytotoxicity against human PBMC cells by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Cytotoxicity against human PBMC cells by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    PBMC IC50
    0.1 μM
    Compound: 1
    Inhibition of TNF-alpha production in LPS-stimulated human PBMC preincubated for 1 hr before LPS challenge measured after 28 to 20 hrs by ELISA
    Inhibition of TNF-alpha production in LPS-stimulated human PBMC preincubated for 1 hr before LPS challenge measured after 28 to 20 hrs by ELISA
    [PMID: 23168019]
    PBMC IC50
    100 nM
    Compound: 1
    Antiinflammatory activity in human PBMC cells assessed as reduction in LPS-induced TNF-alpha production preincubated for 1 hr followed by LPS addition and measured after 18 to 20 hrs by ELISA
    Antiinflammatory activity in human PBMC cells assessed as reduction in LPS-induced TNF-alpha production preincubated for 1 hr followed by LPS addition and measured after 18 to 20 hrs by ELISA
    [PMID: 31125896]
    Raji IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human Raji cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human Raji cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    RPMI-8226 IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human RPMI8226 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human RPMI8226 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    T-cell EC50
    0.15 μM
    Compound: 1
    Inhibition of IL-2 production in human T cells measured after 2 to 3 days by ELISA
    Inhibition of IL-2 production in human T cells measured after 2 to 3 days by ELISA
    [PMID: 23168019]
    THP-1 IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human THP1 cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human THP1 cells measured after 168 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    U-266 IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human U266 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human U266 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    WI-38 IC50
    > 20 μM
    Compound: Lenalidomide
    Cytotoxicity against human WI38 cells after 72 hrs by MTS assay
    Cytotoxicity against human WI38 cells after 72 hrs by MTS assay
    [PMID: 29795767]
    Z-138 IC50
    > 20000 nM
    Compound: 1
    Antiproliferative activity against human Z138 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    Antiproliferative activity against human Z138 cells measured after 72 hrs by CellTiter96 Aqueous non-radioactive cell proliferation assay
    [PMID: 31125896]
    In Vitro

    Lenalidomide is potent in stimulating T cell proliferation and IFN-γ and IL-2 production. Lenalidomide has been shown to inhibit production of pro inflammatory cytokines TNF-α, IL-1, IL-6, IL-12 and elevate the production of anti-inflammatory cytokine IL-10 from human PBMCs. Lenalidomide downregulates the production of IL-6 directly and also by inhibiting multiple myeloma (MM) cells and bone marrow stromal cells (BMSC) interaction, which augments the apoptosis of myeloma cells[2]. Dose-dependent interaction with the CRBN-DDB1 complex is observed with Thalidomide, Lenalidomide and Pomalidomide, with IC50 values of ~30 μM, ~3 μM and ~3 μM, respectively, These reduced CRBN expression cells (U266-CRBN60 and U266-CRBN75) are less responsive than the parental cells to antiproliferative effects Lenalidomide across a dose-response range of 0.01 to 10 μM[3]. Lenalidomide, a thalidomide analog, functions as a molecular glue between the human E3 ubiquitin ligase cereblon and CKIα is shown to induce the ubiquitination and degradation of this kinase, thus presumably killing leukemic cells by p53 activation[5].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    In Vivo

    The toxicity of Lenalidomide doses up to 15, 22.5, and 45 mg/kg via IV, IP, and PO routes of administration. Limited by solubility in our PBS dosing vehicle, these maximum achievable Lenalidomide doses are well tolerated with the exception of one mouse death (of four total dosed) at the 15 mg/kg IV dose. Notably, no other toxicities are observed in the study at IV doses of 15 mg/kg (n=3) or 10 mg/kg (n=45) or at any other dose level through IV, IP, and PO routes[4].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    Molecular Weight

    259.26

    Formula

    C13H13N3O3

    CAS No.
    Appearance

    Solid

    Color

    Off-white to light yellow

    SMILES

    O=C1C2=CC=CC(N)=C2CN1C(C(N3)=O)CCC3=O

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (385.71 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (9.64 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (9.64 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

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    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.95%

    References
    Cell Assay
    [3]

    Cell lines NCI-H929 and U266, and DF15 cells are grown in RPMI-I640 medium containing 10% (V/V) heat-inactivated fetal bovine serum supplemented with 2 mM glutamine. To produce Lenalidomide resistant cell lines, NCI-H929 cells are treated continuously (fresh Lenalidomide is added every 3-4 days) with control (final 0.1% DMSO) or low-dose Lenalidomide (1 μM) for 2 months until the proliferation of cells is no longer inhibited by Lenalidomide (1 μM), as determined by cell viability (Vi-cell XR cell viability analyzer), cell proliferation by flow cytometry and cell cycle analysis (propidium iodide staining). After acquisition of resistance to 1 μM, the resistant H929 cell lines are treated with Lenalidomide (10 μM) for a further 4 months. After this period of time, the cell cultures achieved fully establish resistance up to high-dose Lenalidomide (30 μM). Prior to the experiments described here, H929 Lenalidomide-resistant cells are taken out of culture with compounds for 5-7 days before use[3].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [4]

    Mice[4]
    Imprinting control region (ICR) mice 8-10 weeks of age are used. Lenalidomide is incompletely soluble at 3.5 mg/mL and above in PBS containing 1% HCl, as visible particulates remained after thorough mixing. Therefore 3 mg/mL is selected as the maximum dosing solution concentration (with no visible particulates). Single, individual mice are initially dosed with 3, 10, or 15 mg/kg IV; 4.5, 15, or 22.5 mg/kg IP; and 9, 30, or 45 mg/kg PO. Additional mice (n=4) are then evaluated at the maximum dose achievable by volume and solubility of Lenalidomide in the dosing solution. All mice are monitored closely for 1 h and re-evaluated for toxicities 3, 6, and 24 h postdose[4].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 3.8571 mL 19.2857 mL 38.5713 mL 96.4283 mL
    5 mM 0.7714 mL 3.8571 mL 7.7143 mL 19.2857 mL
    10 mM 0.3857 mL 1.9286 mL 3.8571 mL 9.6428 mL
    15 mM 0.2571 mL 1.2857 mL 2.5714 mL 6.4286 mL
    20 mM 0.1929 mL 0.9643 mL 1.9286 mL 4.8214 mL
    25 mM 0.1543 mL 0.7714 mL 1.5429 mL 3.8571 mL
    30 mM 0.1286 mL 0.6429 mL 1.2857 mL 3.2143 mL
    40 mM 0.0964 mL 0.4821 mL 0.9643 mL 2.4107 mL
    50 mM 0.0771 mL 0.3857 mL 0.7714 mL 1.9286 mL
    60 mM 0.0643 mL 0.3214 mL 0.6429 mL 1.6071 mL
    80 mM 0.0482 mL 0.2411 mL 0.4821 mL 1.2054 mL
    100 mM 0.0386 mL 0.1929 mL 0.3857 mL 0.9643 mL
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