2. Metabolic Enzyme/Protease Apoptosis PROTAC
  3. E1/E2/E3 Enzyme Apoptosis Molecular Glues
  4. 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 (CC 122) is an orally active cereblon modulator. Avadomide modulates cereblon E3 ligase activity and induces apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines. Avadomide exhibits potent antitumor and immunomodulatory activities.

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Avadomide Chemical Structure

Avadomide Chemical Structure

CAS No. : 1015474-32-4

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Based on 6 publication(s) in Google Scholar

Other Forms of Avadomide:

Avadomide Related Antibodies

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Description

Avadomide (CC 122) is an orally active cereblon modulator. Avadomide modulates cereblon E3 ligase activity and induces apoptosis of diffuse large B-cell lymphoma (DLBCL) cell lines. Avadomide exhibits potent antitumor and immunomodulatory activities[1][2].

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.

Avadomide Related Antibodies
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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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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Avadomide Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    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.

Keywords:

Avadomide1015474-32-4CC 122CC122CC-122E1/E2/E3 EnzymeApoptosisMolecular GluesE1 activating enzymeE2 conjugating enzymeE3 ligating enzymeUbiquitin activating enzymeUbiquitin conjugating enzymeUbiquitin ligaseorallycereblonE3ligaseantitumorimmunomodulatorydiffuselargeB-celllymphomaDLBCLInhibitorinhibitorinhibit

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