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INK 128 (MLN0128)

现货
Catalog No.
A8551
MTOR(TORC-1/-2)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 900.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,000.00
现货
50mg
¥ 2,500.00
现货

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Background

INK 128 (MLN0128) is a selective inhibitor of mTOR with IC50 value of 1 nM [3].

mTOR (mammalian target of rapamycin) is an evolutionarily conserved serine/threonine kinase which combined PI3K/AKT/mTOR pathway and plays an important role in regulating many fundamental features of cell growth and division [1].

INK 128 (MLN0128) is a potent mTOR inhibitor. When tested with human pancreatic cancer cells, INK-128 treatment inhibited cell growth and survival via inhibiting mTOR in a time- and concentration- dependent manner [2]. In HER2-positive breast cell lines, INK 128 treatment significantly delayed cell cycle and inhibited cell proliferation through inhibiting mTOR [1].

In a ZR-75-1 breast cancer xenograft model, INK128 treatment in a dose of 0.3mg/Kg/day significantly inhibited tumor growth. When combined with other standard targeted therapy or chemotherapy such as sorafenib, sutent and paclitaxel, enhanced anti-tumor growth activity was observed. INK128 is reported to have excellent physiochemical properties and is currently undergoing preclinical evaluation [3]. When tested with MDA-MB361 mouse model, administration of INK 128 showed a resistance after 20 days, and combined with lapatinib resulted in long-lasting tumor regression [1].

References:
[1].  Garcia-Garcia, C., et al., Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy. Clin Cancer Res, 2012. 18(9): p. 2603-12.
[2].  Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8.
[3].  Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009.

文献引用

1. Samluk L, Urbanska M, et al. "Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress." Mol Biol Cell. 2019 Jul 15;30(15):1864-1877. PMID:31116686
2. Topf U, Suppanz I, et al. "Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species." Nat Commun. 2018 Jan 22;9(1):324. PMID:29358734
3. Dite TA, Ling NXY, et al. "The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs." Nat Commun. 2017 Sep 18;8(1):571. PMID:28924239
4.Robert R. Redfield,Alonso Heredia,et al. "Treatment agents for inhibiting hiv and cancer in hiv infected patients." Google Patents.2016.
5.Heredia, Alonso, et al. "Targeting of mTOR catalytic site inhibits multiple steps of the HIV-1 lifecycle and suppresses HIV-1 viremia in humanized mice." Proceedings of the National Academy of Sciences (2015): 201511144. PMID:26170311

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt309.33
Cas No.1224844-38-5
FormulaC15H15N7O
SynonymsINK128; INK-128
Solubility≥15.45mg/mL in DMSO
Chemical Name5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine
SDFDownload SDF
Canonical SMILESCC(C)N1C2=C(C(=N1)C3=CC4=C(C=C3)OC(=N4)N)C(=NC=N2)N
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

激酶实验 [1]:

激酶实验

使用LanthaScreen激酶试剂盒试剂测定mTOR活性。使用PI(3)KHTRF测定试剂盒测定PI(3)K α、β、γ和δ活性。使用20 μM ~ 0.1 nM的浓度(12点曲线)计算INK 128抑制50%酶活性所需的浓度 (IC50)。使用非线性回归模型测定IC50值。

细胞实验 [2]:

细胞系

PANC-1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 °C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 °C可放置数月。

反应条件

10 ~ 100 nM;72小时

实验结果

INK 128呈时间和剂量依赖性地抑制PANC-1细胞存活。此外,在10 ~ 100 nM浓度下,INK 128显著降低PANC-1细胞活力。经INK 128处理48小时后显著降低细胞活力。

动物实验 [3]:

动物模型

ZR-75-1乳腺癌异种移植瘤模型

给药剂量

0.3 mg/kg/day;口服给药

实验结果

在ZR-75-1乳腺癌异种移植瘤模型中,INK 128显著抑制肿瘤生长。INK 128与其它标准靶向治疗或化疗(如:Sorafenib、Sutent和Paclitaxel)药物联合使用可以增强抗肿瘤生长活性。

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]. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, Wang S, Ren P, Martin M, Jessen K, Feldman ME, Weissman JS, Shokat KM, Rommel C, Ruggero D. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012 Feb 22;485(7396):55-61.

[2]. Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8.

[3]. Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009.

生物活性

描述 INK 128 (MLN0128)是一种有效的和选择性的mTOR抑制剂,IC50值为1 nM。
靶点 mTOR PI3Kα PI3Kγ PI3Kδ PI3Kβ  
IC50 1 nM (Ki=1.4 nM) 219 nM 221 nM 230 nM 5293 nM  

质量控制

质量控制和MSDS

批次:

化学结构

INK 128 (MLN0128)

相关生物数据

INK 128 (MLN0128)

相关生物数据

INK 128 (MLN0128)

相关生物数据

INK 128 (MLN0128)