Home Ubiquitin E3 Ligase inhibitor - Immunology & Inflammation related modulator Avadomide (CC-122)

research use only

Avadomide (CC-122) E3 Ligase inhibitor

Cat.No.S7892

Avadomide (CC-122) is a new chemical entity termed pleiotropic pathway modifier and a novel agent for Diffuse large B-cell lymphoma (DLBCL) with antitumor and immunomodulatory activity. Its molecular target is the protein cereblon (CRBN), a substrate receptor of the cullin ring E3 ubiquitin ligase complex CRL4CRBN.
Avadomide (CC-122) E3 Ligase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 286.29

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Chemical Information, Storage & Stability

Molecular Weight 286.29 Formula

C14H14N4O3

 Storage (From the date of receipt)
CAS No. 1015474-32-4 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC1=NC2=CC=CC(=C2C(=O)N1C3CCC(=O)NC3=O)N

Solubility

In vitro
Batch:

DMSO : 57 mg/mL (199.09 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 1 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg
g
μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO
%
% Tween 80
% ddH2O
% DMSO
+
%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC50/Ki
CRBN [1]
In vitro
Avadomide (CC-122) is a novel agent for DLBCL with antitumor and immunomodulatory activity. In DLBCL cell lines, it binds CRBN and induces degradation or short hairpin RNA-mediated knockdown of Aiolos and Ikaros which correlates with increased transcription of interferon (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 cell lines. CRBN is the molecular target of this compound, which recruits Aiolos/Ikaros to CRL4CRBN upon binding to CRBN, and E3 ligase enzymatic activity is necessary for ubiquitination of Aiolos and Ikaros and thus their proteasomal degradation induced by CC-122. It induces IFN-regulated proteins and its mediated effects on the IFN pathway is independent of autocrine type I and II IFN secretion and signaling[1].
In vivo
Avadomide (CC-122) reduces tumor growth in xenograft models established from ABC- and GCB-DLBCL cell lines, and stimulates IL-2 production in primary T cells. Also, in a single-arm clinical trial of this compound, exposure to it reduced expression levels of Aiolos and Ikaros in each patient by 25% to 50% demonstrating the utility of these 2 proteins as pharmacodynamic markers of CC-122[1].
References

Applications

Methods Biomarkers Images PMID
Western blot CRBN Aiolos / Ikaros S7892-WB1 26002965

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05688475 Active not recruiting
Non-Hodgkin Lymphoma
Bristol-Myers Squibb
 April 11 2023 Phase 1
NCT03834623 Completed
Melanoma
H. Lee Moffitt Cancer Center and Research Institute|Bristol-Myers Squibb|Celgene Corporation
 May 14 2019 Phase 2
NCT02406742 Completed
Leukemia Lymphocytic Chronic B-Cell
Celgene
 July 27 2015 Phase 1|Phase 2
NCT02234999 Completed
Healthy Volunteers
Celgene
 September 23 2014 Phase 1
NCT01421524 Completed
Multiple Myeloma|Lymphoma Large B-Cell Diffuse|Pleiotropic Pathway Modifier|Glioblastoma|Lymphoma|Primary Central Nervous System Lymphoma
Celgene
 September 12 2011 Phase 1

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Signaling Pathway Map