LCL161 is a SMAC mimetic, an IAP antagonist with oral activity that inhibits XIAP (IC50=35 nM) in HEK293 cells and also inhibits cIAP1 (IC50=0.4 nM) in MDA-MB-231 cells. LCL161 has potential antitumor activity.

XIAP (HEK293 cells):35 nM, CIAP1 (MDA-MB-231 cells):0.4 nM

方法：MOLM13 细胞用 LCL161 (1000-160000 nM) 和 PKC412 (2.5-40 nM) 处理 3 天，通过 trypan blue exclusion 检测细胞活力。
结果：当单独给药时，LCL161 适度抑制细胞的生长。LCL161 和 PKC412 联合治疗 MOLM13-luc+ 细胞比单独使用任何一种药物都能显著杀死更多的细胞，Calcusyn 联合指数表明存在协同作用。[1]
方法：NSCLC 细胞 A549 和 H460 用 LCL161 (10 µM) 和 paclitaxel (10 µM) 处理 48 h，flow cytometry 检测细胞凋亡。
结果：与单独用 LCL161 或 paclitaxel 治疗的细胞相比，LCL161/paclitaxel 联合治疗组的细胞凋亡显著降低。[2]

方法：为检测体内抗肿瘤活性，将 LCL161 (50 mg/kg，每天两次) 和 PKC412 (40 mg/kg，每天一次) 灌胃给药给注射 Ba/F3-FLT3-ITD-luc+ 肿瘤细胞的 NCr nude 小鼠，给药七天。
结果：LCL161 显著增强了 PKC412 在体内抑制 Ba/F3-FLT3-ITD-luc+ 细胞生长的能力。PKC412 或 LCL161 单独抑制白血病生长与 PKC412+LCL161 联合抑制白血病生长之间的差异也很显著。PKC412+LCL161 治疗的小鼠的脾脏重量百分比小于单独使用载体或任何一种药物治疗的小鼠。[1]

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].

In vitro testing is performed using DIMSCAN (Only for Reference)