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SBI-0206965

现货
Catalog No.
A8715
ULK1抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 1,000.00
现货
25mg
¥ 3,500.00
现货

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Background

SBI-0206965 is a novel inhibitor of the autophagy-initiating kinase ULK1.

ULK1 (Unc-51 like Autophagy Activating Kinase 1) is a serine/threonine-protein kinase involved in autophagy in starvation. It is an AMPK regulator, a downstream effector and negative regulator of mTORC1. It also plays a role in neuronal differentiation. [1]

In A549 cells, 5 mM SBI-0206965 strongly suppresses the AZD8055 induced autophagy effect. In SBI-0206965 treated MEFs, after 18 hours of amino acid deprivation, 42% of 6965-treated cells shows 7-AAD and AnnexinV (end stage apoptosis). SBI-02066965 also promotes apoptosis

in the nutrient-starved state in human U87MG glioblastoma cells and in murine lung carcinoma cells. Moreover, 5 mM SBI-0206965 triggers apoptosis in 23% of cells when combined with AZD8055 versus 10% of cells in the absence of AZD8055 and 7% of cells treated with AZD8055

alone. Similar to AZD8055, both rapamycin and INK128 exhibits a mild apoptotic response on their own in A549 cells but significantly enhances this apoptotic response when combined with SBI-0206965. [1]

Reference:
1.  Egan DF, Chun MG, Vamos M et al. Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates. Mol Cell. 2015 Jul 16;59(2):285-97.

文献引用

1. Dite TA, Langendorf CG, et al. "AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965." J Biol Chem. 2018 Jun 8;293(23):8874-8885. PMID:29695504
2. 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

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt489.32
Cas No.1884220-36-3
FormulaC21H21BrN4O5
Solubility≥24.5mg/mL in DMSO
Chemical Name(Z)-2-((5-bromo-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzimidic acid
SDFDownload SDF
Canonical SMILESC/N=C(O)/C1=CC=CC=C1OC2=NC(NC3=CC(OC)=C(OC)C(OC)=C3)=NC=C2Br
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

转染WT或KI Myc标记的ULK1以及WT Vps34的HEK293T细胞

制备方法

在DMSO中的溶解度大于24.5mg/mL。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

1、10和50 μM;1小时

实验结果

在转染WT或KI Myc标记的ULK1以及WT Vps34的HEK293T细胞中,SBI-0206965在约5 μM的剂量下抑制过表达Vps34的Ser249磷酸化。据发现,在HEK293T细胞中,SBI-0206965也对Beclin1 Ser15显示相当的磷酸化抑制作用。

References:

[1]. Egan DF, Chun MG, Vamos M et al. Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates. Mol Cell. 2015 Jul 16;59(2):285-97.

质量控制

化学结构

SBI-0206965

相关生物数据

SBI-0206965

相关生物数据

SBI-0206965