Avadomide (CC-122)，一种新型的多效性修饰剂化合物，在弥漫性大B细胞淋巴瘤（DLBCL）中具有抗肿瘤、免疫调节活性。其分子靶标为cereblon (CRBN)，CRBN是E3泛素化连接酶复合体CRL4CRBN的底物受体。 Information Avadomide (CC-122) 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 CRL4 CRBN . Targets CRBN 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 CRL4 CRBN , 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. 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. Cell Research(from reference) 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\u2009000 nM Incubation Time：5 days
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Avadomide
CAS number：1015474-32-4 molecular formula：C14H14N4O3
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| Chinese alias | 3-(5-氨基-2-甲基-4-氧代喹唑啉-3(4H)-基)-哌啶-2,6-二酮 | 阿伐多胺 | ||
| English alias | 2,6-Piperidinedione, 3-(5-amino-2-methyl-4-oxo-3(4H)-quinazolinyl)- | BDBM76986 | SCHEMBL282749 | 5,8-Dihydro-5,8-dioxo-6-(phenylamino)quinoline | CCG-267340 | MFCD29919294 | 28DZS29F59 | CC-122Avadomide | Emmatos | BP-27973 | GTPL10522 | BCP15938 | MAFEN | ||
| CAS number | 1015474-32-4 | molecular formula | C14H14N4O3 |
| molecular weight | 286.29 g/mol | Exact mass | - |
| PSA | 105.000 Ų | logp | -0.477 |
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