受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C14H14N4O3 |
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分子量 | 286.29 | CAS No. | 1015474-32-4 | |
Solubility (25°C)* | 体外 | DMSO | 57 mg/mL (199.09 mM) | |
Water | Insoluble | |||
Ethanol | 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. |
製品説明 | 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. |
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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]. |
細胞アッセイ | 細胞株 | DLBCL cell lines(TMD8, U2932, Riva, and OCI-LY10) and GCB-DLBCL lines (Karpas 422, WSU-DLCL2, SUDHL-4, OCI-LY19, and Pfeiffer) |
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濃度 | 0.01 to 10 000 nM | |
反応時間 | 5 days | |
実験の流れ | 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 | |
動物実験 | 動物モデル | CB-17 SCID mice |
投薬量 | 3 or 30 mg/kg | |
投与方法 | p.o. |
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 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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