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

IKK2:30 nM

在SCID-beige移植瘤小鼠模型中,LY2409881（50/100/200 mg/kg,i.p.）可显著抑制肿瘤生长.

LY240988对卵巢癌SKOV3细胞株具有中等毒性。在弥漫性大B细胞淋巴瘤细胞中,LY2409881对激活的NF-?B有抑制作用,浓度和时间依赖性地抑制细胞生长并使细胞凋亡。在SUDHL2细胞中,LY2409881可协同环磷酰胺和阿霉素抑制细胞生长,但对LY1细胞无协同效果。在SUDHL22和LY1细胞中,组蛋白去乙酰化酶抑制剂罗米地辛与LY2409881可协同抑制细胞生长。

CYP3A activity is assessed using the probe reactions, midazolam-1′-hydroxylation and testosterone 6β-hydroxylation. For reversible inhibition, incubations (37°C, 10 min) are composed of (final concentrations): potassium phosphate buffer (100 mM, pH 7.4), β-NADPH (1 mM), magnesium chloride (5 mM), microsomal protein (0.025 mg/mL), probe substrate (1 μM midazolam or 25 μM testosterone), LCL161 (0, 0.5, 1, 5, 10, 25, 50, or 100 μM) and organic solvent (0.2% acetonitrile for midazolam, 0.2% methanol for testosterone). After a 3-minute preincubation, the reactions are initiated by addition of β-NADPH and terminated by addition of acetonitrile (two volumes). Reactions are previously shown to be linear with respect to time and protein concentration (results not shown) with midazolam and testosterone turnover of 8.7±1.3% (n=3) and 2.6±0.20%, respectively. Formation of 1′-hydroxymidazolam and 6β-hydroxytestosterone is determined by LC-MS/MS as described below[3].

Cytotoxicity is evaluated using the CellTiter-Glo Reagent according to the manufacturer's manual. Experiments are carried out in 96-well plates, with each treatment in triplicate. Samples are taken at typically 24, 48, and 72 hours after treatment. Cytotoxicity is expressed by the decreasing percentage of live cells in each treatment relative to the untreated control from the same experiment. IC50 for each cell line is calculated using the CalcuSyn Version 2.0 software.(Only for Reference)