LY2409881 trihydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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

LY2409881 trihydrochloride is a novel selective inhibitor of IKK2 with IC50 of 30 nM; IC50 for IKK1 and other common kinases is at least one log higher.

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.

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).

LY2409881 | LY-2409881 | LY 2409881

Immunology/Inflammation

IκB kinase (IKK)

IKK2

Cancer

——

946518-60-1

594.43

C24H32Cl4N6OS

>98% (HPLC)

DMSO: 20 mg/mL warmed (33.64 mM)

O=C(C1=C(C=C(C2=NC(NCCCN3CCN(CC3)C)=NC=C2Cl)S4)C4=CC=C1)NC5CC5

2-(5-chloro-2-((3-(4-methylpiperazin-1-yl)propyl)amino)pyrimidin-4-yl)-N-cyclopropylbenzo[b]thiophene-4-carboxamide

(-20℃)

With Ice Pack

≥ 2 years