Avadomide

SKU: orb1304076

Description

Avadomide (CC-122) is an orally bioavailable cereblon-modulating agent with potential antineoplastic properties. It is utilized in cancer research, particularly in hematological malignancies, to study its immunomodulatory and tumoricidal effects in both in vitro and in vivo experimental models.

Research Area

Cell Biology, Pharmacology & Drug Discovery, Protein Biochemistry, Signal Transduction

Key Properties

• CAS Number: 1015474-32-4
• MW: 286.29
• Purity: 99.56% (May vary between batches)
• Formula: C₁₄H₁₄N₄O₃
• SMILES: Cc1nc2cccc(N)c2c(=O)n1C1CCC(=O)NC1=O
• Target: Molecular Glues,Ligands for E3 Ligase,E1/E2/E3 Enzyme,NF-κB,Apoptosis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (6.99 mM);Ethanol:1 mg/mL (3.49 mM);DMSO:52 mg/mL (181.63 mM)

Bioactivity

• In Vivo:
  Avadomide 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 Avadomide Clinicalal trial, exposure to Avadomide 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 Avadomide.
• In Vitro:
  Avadomide 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 Avadomide, Avadomide binding to CRBN recruits Aiolos/Ikaros to CRL4CRBN, and E3 ligase enzymatic activity is necessary for ubiquitination of Aiolos and Ikaros and thus their proteasomal degradation induced by Avadomide. Avadomide induces IFN-regulated proteins and its mediated effects on the IFN pathway is independent of autocrine type I and II IFN secretion and signaling.
• Cell Research:
  Diffuse Large B-Cell Lymphoma are cultured in RPMI-1640 containing 10-20% fetal bovine serum, 1% Penicillin/Streptomycin and 1 mM sodium pyruvate. 2×104 cells are plated per well in media containing either DMSO or various concentrations of CC-122. Cells are cultured for 5 days at 37 degrees Celsius after which tritiated thymidine is added to the cell culture for the final 6 hours. Cells are subsequently harvested onto filter plates. After the plates have dried, scintillation fluid is added to the plates and read on a Top-count reader(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

diffuse, DLBCL, E2Enzyme, E3 Enzyme, E3 Ligase, E2 conjugating enzyme, E2 Enzyme, E1Enzyme, E1 Enzyme, E1/E2/E3 Enzyme, E1 activating enzyme, CC 122, CC-122, CC122, cereblon, Apoptosis, Avadomide, antitumor, B-cell, Inhibitor, large, E3 ligating enzyme, E3Enzyme, LigandforE3Ligase, ligase, Ligand for E3 Ligase, inhibit, immunomodulatory, lymphoma, orally, Ubiquitin conjugating enzyme, Ubiquitin ligase, Ubiquitin activating enzyme

Compound Identifiers

PubChem CID

24967599