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Avadomide (CC-122) E3 Ligase inhibitor

Name: Avadomide (CC-122)
Brand: Selleck Chemicals
SKU: S7892
Availability: InStock
Rating: 5 (5 reviews)

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 CRL4^CRBN.

Chemical Structure

Molecular Weight: 286.29

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Quality Control

Batch: Purity: 99.87%

99.87

Related Targets	Proteasome E1 Activating DUB p97 SUMO E2 conjugating
Other E3 Ligase Inhibitors	Iberdomide (CC-220) Skp2 inhibitor C1 (SKPin C1) Apcin PRT4165 Mezigdomide (CC-92480) VL285 SZL P1-41 VH298 Homo-PROTAC cereblon degrader 1 CC-885

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
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

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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

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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.

Chemical Information, Storage & Stability

Molecular Weight	286.29	Formula	C₁₄H₁₄N₄O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1015474-32-4	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=NC2=CC=CC(=C2C(=O)N1C3CCC(=O)NC3=O)N

Mechanism of Action

Targets/IC₅₀/Ki	CRBN
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 CRL4^CRBN 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.
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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/26002965/

Applications

Methods	Biomarkers	Images	PMID
Western blot	CRBN Aiolos / Ikaros		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

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