Avadomide (CC-122)

Catalog No.S7892 Batch:S789201

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Technical Data

Formula

C14H14N4O3

Molecular Weight 286.29 CAS No. 1015474-32-4
Solubility (25°C)* In vitro DMSO 57 mg/mL (199.09 mM)
Ethanol 1 mg/mL (3.49 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Avadomide (CC-122), a new chemical entity termed pleiotropic pathway modifier, is 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.
Targets
CRBN [1]
In vitro 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 CC-122, CC-122 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 CC-122. CC-122 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 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 CC-122 clinical trial, exposure to CC-122 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].

Protocol (from reference)

Cell Assay:[1]
  • Cell lines

    DLBCL cell lines(TMD8, U2932, Riva, and OCI-LY10) and GCB-DLBCL lines (Karpas 422, WSU-DLCL2, SUDHL-4, OCI-LY19, and Pfeiffer)

  • Concentrations

    0.01 to 10 000 nM

  • Incubation Time

    5 days

  • Method

    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

Animal Study:[1]
  • Animal Models

    CB-17 SCID mice

  • Dosages

    3 or 30 mg/kg

  • Administration

    p.o.

Selleck's Avadomide (CC-122) has been cited by 5 publications

Degradome analysis to identify direct protein substrates of small-molecule degraders [ bioRxiv, 2024, 10.1101/2024.01.28.577572] PubMed: none
Lenalidomide bypasses CD28 co-stimulation to reinstate PD-1 immunotherapy by activating Notch signaling [ Cell Chem Biol, 2022, S2451-9456(22)00204-5] PubMed: 35732177
IRF4 modulates the response to BCR activation in chronic lymphocytic leukemia regulating IKAROS and SYK [ Leukemia, 2021, 35(5):1330-1343] PubMed: 33623139
A Cereblon Modulator CC-885 Induces CRBN- and p97-Dependent PLK1 Degradation and Synergizes with Volasertib to Suppress Lung Cancer [ Mol Ther Oncolytics, 2020, 18:215-225] PubMed: 32728610
Genome-wide CRISPR screens reveal genetic mediators of cereblon modulator toxicity in primary effusion lymphoma. [ Blood Adv, 2019, 3(14):2105-2117] PubMed: 31300418

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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