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LCL161

现货
Catalog No.
A3541
IAPs拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,200.00
现货
5mg
¥ 1,100.00
现货
10mg
¥ 1,600.00
现货
50mg
¥ 5,000.00
现货
100mg
¥ 7,400.00
现货

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Background

LCL161 is a small molecular antagonist of the inhibitor of apoptosis (IAP) with IC50 value of 10.23 μM in Hep3B cells [1].
IAP is a family of proteins which are firstly found in virus and to inhibit the apoptosis of the infected hosts. It contains eight proteins in human. Since they were always found to overexpress in variety of malignant tumors, the IAP are thought to be appropriate targets in cancer therapy. SMAC (second mitochondria-derived activator of caspases) is the first-identified antagonist of IAP. It binds to XIAP within the BIR2/3 domain through its N-terminal segment. As a mimetic of SMAC, LCL161 is designed to be the inhibitor of both XIAP and cIAP1/2 [1].
LCL161 showed significant inhibition of cell proliferation and viability in two human hepatocellular carcinoma (HCC) cells, Hep3B and PLC5. The IC50 values were 10 and 19 μM, respectively. However, LCL161 had no effect in the two other HCC cell lines, Sk-Hep1 (IC50 value of 224 μM) and Huh-7 (IC50 value of 228 μM). The difference of the effects is found to dependent on the expression of Bcl-2 in cells. For the ALL cells, LCL161 exerted growth inhibition with IC50 values of 9.3 and 0.25 μM, respectively. LCL161 also showed effect on the ALCL cell line Karpas-299 with IC50 value of 1.6 μM [1, 2].
In vivo, LCL161 markedly affected the distribution of EFS in many solid tumor xenograft models. It also caused growth delay in some tumors such as osteosarcoma, neuroblastoma and glioblastoma at dose of 30 mg/kg orally. Besides that, LCL161 administration caused significant growth inhibition in EW-5 and BT-39 glioblastoma but not in BT-28. Moreover, the combination therapy of LCL161 and the adeno-associated virus bacteriophage-tumor necrosis factor-α (AAVP-TNF-α) has been reported to has synergistic anti-tumor effects and delayed treatment resistance in mice models of tumor xenografts [1, 2 and 3].
References:
1.Chen K F, Lin J P, Shiau C W, et al. Inhibition of Bcl-2 improves effect of LCL161, a SMAC mimetic, in hepatocellular carcinoma cells. Biochemical pharmacology, 2012, 84(3): 268-277.
2.Houghton P J, Kang M H, Reynolds C P, et al. Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program. Pediatric blood & cancer, 2012, 58(4): 636-639.
3.Yuan Z, Syrkin G, Adem A, et al. Blockade of inhibitors of apoptosis (IAPs) in combination with tumor-targeted delivery of tumor necrosis factor-α leads to synergistic antitumor activity. Cancer gene therapy, 2012, 20(1): 46-56.

文献引用

1. Gradzka S, Thomas OS, et al. "Inhibitor of apoptosis proteins are required for effective fusion of autophagosomes with lysosomes." Cell Death Dis. 2018 May 9;9(5):529. PMID:29743550

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt500.63
Cas No.1005342-46-0
FormulaC26H33FN4O3S
SynonymsLCL-161;LCL 161
Solubility≥25.05 mg/mL in DMSO, <2.58 mg/mL in EtOH, <2.45 mg/mL in H2O
Chemical Name(2S)-N-[(1S)-1-cyclohexyl-2-[(2S)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide
SDFDownload SDF
Canonical SMILESCC(C(=O)NC(C1CCCCC1)C(=O)N2CCCC2C3=NC(=CS3)C(=O)C4=CC=C(C=C4)F)NC
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

Hep3B、PLC5、Sk-Hep1和Huh-7细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

0、0.01、0.05、0.1、0.5、1、5和10 μM;24、48或72小时

实验结果

在2种人肝细胞癌(HCC)细胞中,即Hep3B和PLC5细胞,LCL161显著抑制细胞增殖与活性。其IC50值分别为10 μM和19 μM。然而,LCL161对其它2种HCC细胞系(对SK-HEP1细胞的IC50值为224 μM;对Huh-7细胞的IC50值为228 μM)无影响。

动物实验 [1]:

动物模型

Huh-7细胞异种移植瘤裸鼠模型

给药剂量

50 mg/kg;口服给药;每日1次,持续20日

实验结果

LCL161和SC-2001联合用药显著抑制Huh-7肿瘤细胞,同时不会显著影响体重。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Chen K F, Lin J P, Shiau C W, et al. Inhibition of Bcl-2 improves effect of LCL161, a SMAC mimetic, in hepatocellular carcinoma cells. Biochemical pharmacology, 2012, 84(3): 268-277.

质量控制

化学结构

LCL161

相关生物数据

CORM-3