LCL161 是一种 SMAC 模拟物，可有效结合并抑制多种 IAP。它抑制 HEK293 细胞中XIAP和 MDA-MB-231细胞中cIAP1的IC50分别为 35 和 0.4 nM。

LCL161, a SMAC mimetic, effectivity binds to and inhibits multiple IAPs (i.e. XIAP, c-IAP).

尼罗替尼与LCL161联用对白血病生长的抑制具有累加作用.LCL161（100 mg/kg）增强尼罗替尼（100 mg/kg）对患有白血病小鼠的体内作用.LCL161使PKC412对Ba/F3-FLT3-ITD-luc+细胞体内生长的抑制作用显著增强.LCL161能够与阿霉素和阿糖胞苷（标准化疗剂）阳性结合,抗FLT3-ITD和D835Y表达细胞.

LCL161可适度抑制表达FLT3-ITD的细胞生长,IC50的范围为0.5 μM (Ba/F3-FLT3-ITD 细胞)到4 μM (MOLM13-luc+ 细胞)。LCL161对D835Y突变体的抑制能力相当高,测试抗Ba/F3-D835Y细胞时,IC50为50 nM。LCL161与凋亡抑制蛋白因子的结合亲和力高,且可启动对cIAP1/2的破坏,其激活胱天蛋白酶后进而诱导细胞凋亡。LCL161 与PKC412联用对MOLM13-luc+细胞的细胞杀伤力要强于其任何一个单独使用的药剂,Calcusyn复合指数表明其具有协同作用。

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)

1005342-46-0

C26H33FN4O3S

500.63

DMSO:93 mg/mL (185.8 mM)
Ethanol:16 mg/mL (32 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years