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LY2409881

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产品价格:电议      采购度:1606      原产地:美洲

发布时间:2021/7/26 18:18:27      所属地区:上海 上海市

简要描述:

LY2409881 是一种选择性的 IκB 激酶 β (IKK2) 抑制剂,IC50 为 30 nM。

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LY2409881

CAS No. : 946518-61-2

MCE 站:LY2409881

产品活性:LY2409881 是一种选择性的 IκB 激酶 β (IKK2) 抑制剂,IC50 为 30 nM。

研究领域:NF-κB

作用靶点:IKK

In Vitro: LY2409881 is an IKK2 inhibitor that inhibits TNFα-induced activation of NF-κB. By in vitro kinase assay, LY2409881 potently inhibits IKK2, with an IC50 of 30 nM. In contrast, the IC50 for IKK1 and other common kinases is at least one log higher. The specificity of LY2409881 for NF-κB signaling is further studied in a cell-based assay, by examining the effect of LY2409881 in the TNFα-dependent antiapoptosis function. TNFα is a well-characterized upstream stimulus of NF-κB. In the ovarian cancer cell line SKOV3, LY2409881 demonstrates moderate cytotoxicity, whereas TNFα at 10 ng/mL does not cause any cytotoxicity. In contrast, coadministration of LY2409881 and TNFα results in markedly higher cell killing compared with LY2409881. This is because TNFα-dependent activation of antiapoptotic signals mediated by NF-κB is blocked by LY2409881, while the proapoptotic TNF receptor-associated death domain (TRADD) and FAS-associated death domain (FADD) cascade pathways activated by TNFα are not affected by LY2409881.

In Vivo: A well-established xenograft model of DLBCL is used to confirm the activity of LY2409881 in vivo. SCID-beige mice implanted with LY10 cell-derived tumors are given intraperitoneal injections of LY2409881 twice weekly at three different doses: 50, 100, and 200 mg/kg. The treatments are well tolerated, resulting in no death or severe morbidity of the mice. The average tumor volume is graphed as a function of time for each treatment group. The rates of tumor volume growth of the treatment groups are all significantly slower than the untreated control group (P≤0.01).

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更新时间:2024/1/2 10:15:57

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