1. Metabolic Enzyme/Protease Apoptosis PROTAC NF-κB
  2. E1/E2/E3 Enzyme Apoptosis Molecular Glues NF-κB
  3. Avadomide

Avadomide (CC 122) est un modulateur oralement active de cereblon. Avadomide module l'activité de la ligase du cereblon E3 et induit l'apoptose des lignées cellulaires diffuses de lymphome à grandes cellules B (DLBCL). Avadomide présente de puissantes activités antitumorales et immunomodulatrices.

Avadomid (CC 122) ist ein oral aktiver cereblon-Modulator. Avadomid moduliert die Aktivität der Cereblon-E3-Ligase und induziert die apoptosis diffuser großzelliger B-Zell-Lymphom-Zelllinien (DLBCL). Avadomid weist starke antitumorale und immunmodulatorische Aktivitäten auf.

Avadomide is an orally active cereblon modulator. Avadomide modulates cereblon E3 ligase activity, inhibits NF-κB pathway, arrests the cell cycle at G1 phase, and thus induces apoptosis in cancer cell PDAC. Avadomide exhibits potent antitumor and immunomodulatory activities.

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

CAS No. : 1015474-32-4

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Based on 6 publication(s) in Google Scholar

Other Forms of Avadomide:

Top Publications Citing Use of Products

    Avadomide purchased from MedChemExpress. Usage Cited in: Cancer Chemother Pharmacol. 2023 Oct;92(4):303-314.  [Abstract]

    MTT assay showing the anti-tumor effects of Avadomide in four PDAC cell lines. Data are represented as mean of triplicate independent experiments.

    Avadomide purchased from MedChemExpress. Usage Cited in: Cancer Chemother Pharmacol. 2023 Oct;92(4):303-314.  [Abstract]

    Representative dot plots from flow cytometry analysis illustrating apoptotic status by Annexin V assay. Panc1, BcPX3, and PSN1 after treatment with placebo, 10 ng/mL gemcitabine, and 200 μM avadomide for 36 h, respectively.

    Avadomide purchased from MedChemExpress. Usage Cited in: Cancer Chemother Pharmacol. 2023 Oct;92(4):303-314.  [Abstract]

    The effect of Avadomide (200 μM; 36 h) on the protein levels of pIκBα and IκBα in PDAC cells.

    Avadomide purchased from MedChemExpress. Usage Cited in: Cancer Chemother Pharmacol. 2023 Oct;92(4):303-314.  [Abstract]

    Avadomide (0.5 mg/kg). Tumor growth rates varied among different cell lines. MiaPaCa2-GR2 showed the strongest inhibitory effect.

    Avadomide purchased from MedChemExpress. Usage Cited in: Cancer Chemother Pharmacol. 2023 Oct;92(4):303-314.  [Abstract]

    Avadomide (0.5 mg/kg). Hematoxylin-eosin staining of tumor tissue.

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    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Avadomide is an orally active cereblon modulator. Avadomide modulates cereblon E3 ligase activity, inhibits NF-κB pathway, arrests the cell cycle at G1 phase, and thus induces apoptosis in cancer cell PDAC. Avadomide exhibits potent antitumor and immunomodulatory activities[1][2][3].

    Cellular Effect
    Cell Line Type Value Description References
    Daudi EC50
    182.3 nM
    Compound: CC-122
    Antiproliferative activity against human Daudi cells assessed as reduction in cell viability incubated for 2 days by CCK8 assay
    Antiproliferative activity against human Daudi cells assessed as reduction in cell viability incubated for 2 days by CCK8 assay
    [PMID: 36577219]
    HEK-293T EC50
    >10 μM
    Compound: CC-122
    Antiproliferative activity against human HEK-293T cells assessed as reduction in cell viability incubated for 2 days by CCK8 assay
    Antiproliferative activity against human HEK-293T cells assessed as reduction in cell viability incubated for 2 days by CCK8 assay
    [PMID: 36577219]
    MM1.S EC50
    21.91 nM
    Compound: CC-122
    Antiproliferative activity against human MM1.S cells assessed as reduction in cell viability incubated for 2 days by CCK8 assay
    Antiproliferative activity against human MM1.S cells assessed as reduction in cell viability incubated for 2 days by CCK8 assay
    [PMID: 36577219]
    In Vitro

    Avadomide inhibits proliferation and induces apoptosis in ABC and GCB DLBCL. In DLBCL cell lines, Avadomide-induced degradation or short hairpin RNA-mediated knockdown of Aiolos and Ikaros correlates with increased transcription of IFN-stimulated genes independent of IFN-α, -β, and -γ production and/or secretion and results in apoptosis in both activated B-cell (ABC) and germinal center B-cell DLBCL[1].

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

    In Vivo

    Treatment of female CB-17 SCID mice with Avadomide (CC122) at 3 or 30 mg/kg once daily significantly decreased tumor growth in OCI-LY10 ABC-DLBCL (P = .028 and P < .001, respectively) and WSU-DLCL2 GCB-DLBCL derived xenograft models (P < .01) compared with the vehicle control. In a separate study, we assessed the ability of Avadomide (CC122) to promote degradation of Ikaros and Aiolos in vivo. In the 21-day efficacy study of WSU-DLCL2 xenograft transplanted mice, tumors were excised 1, 6, or 24 hours post final dosing. Aiolos and Ikaros expression was interrogated through immunohistochemistry (IHC) and was found to be decreased 64% and 30%, respectively, compared with vehicle within 1 hour of treatment, with a maximal reduction of 94% and 69%, respectively, observed at 6 hours. Aiolos and Ikaros levels partially recovered 24 hours postdosing with protein level within 20% and 34% of vehicle, respectively. The 24-hour postdose Aiolos and Ikaros expression represents the trough compound level following multiple doses of Avadomide (CC122). When the 1-hour time point is compared with the 24-hour postdose time point, there is a significant reduction in Aiolos but not Ikaros expression; however, at the 6-hour time point, both transcription factors are significantly different from the 24-hour time point. Taken together, these data reveal that Avadomide (CC122) inhibited DLBCL tumor growth in vivo and that this activity was associated with the degradation of Aiolos and Ikaros in both ABC- and GCB-DLBCL xenograft models[1].

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

    Clinical Trial
    Molecular Weight

    286.29

    Formula

    C14H14N4O3

    CAS No.
    Appearance

    Solid

    Color

    White to gray

    SMILES

    O=C(C(N1C(C)=NC2=C(C(N)=CC=C2)C1=O)CC3)NC3=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 : 33.33 mg/mL (116.42 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 3.4930 mL 17.4648 mL 34.9296 mL
    5 mM 0.6986 mL 3.4930 mL 6.9859 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.

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

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

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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 (8.73 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.
    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
    References
    Animal Administration

    Female SCID mice (CB17/Icr-Prkdcscid, Charles River) were 8 weeks old, with body weights ranging from 15.0 to 23.2 g, on day 1 of these studies. Each SCID mouse was injected subcutaneously in the right flank with 5x106 OCI-LY10 cells (0.2 ml cell suspension). Tumors were calipered in two dimensions to monitor growth as their mean volume approached 100–150 mm3 . Fourteen days (WSU-DLCL2) or twenty-one days (OCI-LY10) after tumor cell implantation, mice were sorted into treatment groups (n=10/group). Tumors were callipered twice weekly during the study. Avadomide (CC122) was suspended in 0.5% carboxymethyl cellulose: 0.25% Tween-80 in de-ionized water. Vehicle and Avadomide (CC122) were each administered via oral gavage (p.o.) once daily for twenty-eight days (qd x28)[1].

    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 3.4930 mL 17.4648 mL 34.9296 mL 87.3240 mL
    5 mM 0.6986 mL 3.4930 mL 6.9859 mL 17.4648 mL
    10 mM 0.3493 mL 1.7465 mL 3.4930 mL 8.7324 mL
    15 mM 0.2329 mL 1.1643 mL 2.3286 mL 5.8216 mL
    20 mM 0.1746 mL 0.8732 mL 1.7465 mL 4.3662 mL
    25 mM 0.1397 mL 0.6986 mL 1.3972 mL 3.4930 mL
    30 mM 0.1164 mL 0.5822 mL 1.1643 mL 2.9108 mL
    40 mM 0.0873 mL 0.4366 mL 0.8732 mL 2.1831 mL
    50 mM 0.0699 mL 0.3493 mL 0.6986 mL 1.7465 mL
    60 mM 0.0582 mL 0.2911 mL 0.5822 mL 1.4554 mL
    80 mM 0.0437 mL 0.2183 mL 0.4366 mL 1.0916 mL
    100 mM 0.0349 mL 0.1746 mL 0.3493 mL 0.8732 mL
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      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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