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MRT67307 HCl

现货
Catalog No.
A3635
SIK/TBK-1/IKKe抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 800.00
现货
5mg
¥ 770.00
现货
10mg
¥ 1,370.00
现货
50mg
¥ 3,500.00
现货

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Background

MRT67307 is an inhibitor for TBK1, IKKε , MARK1-4 and NUAK1 with IC50 value of 19, 160, 27-52 and 230nM , respectively [1]. It is an inhibitor for ULK1and ULK2 with IC50 value of 45 and 38nM, respectively [2]. Also, it is a salt inducible kinase (SIK) inhibitor with IC50 value of 250, 67 and 430nM for SIK1, SIK2 and SIK3, respectively.
SIKs prevent the formation of regulatory macrophages and their inhibition induces increasing in some markers of regulatory macrophages, such as IL-10 and other anti-inflammatory molecules. IKKε and TBK-1 mediate the phosphorylation of interferon regulatory factor 3 (IRF3).  MARK1 is a Serine/threonine-protein kinase.
In macrophages, MRT67307 prevented the production of IFNβ and the phosphorylation of IRF3 without suppressing the activation of NF-κB, which showed that MRT67307 blocked the induction of  Pellino 1 through inhibiting TBK1/IKKε kinase activity [1] [3]. Also, MRT67307 completely blocked the TBK1- or IKKε-induced decrease in the mobility of Pellino 1 [3]. Exposed macrophages to MRT67307 increased the levels of the anti-inflammatory cytokines IL-1ra and IL-10 and decreased the levels of proinflammatory cytokines (such as IL-6, IL-12, and TNF) in response to bacterial lipopolysaccharide (LPS) [4].
References:
[1]. Clark K, Peggie M, Plater L, et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J, 2011, 434(1): 93-104.
[2]. Petherick KJ, Conway OJ, Mpamhanga C, et al. Pharmacological Inhibition of ULK1 Blocks mTOR-Dependent Autophagy. J Biol Chem, 2015, pii: jbc.C114.627778.
[3]. Smith H, Liu XY, Dai L, et al. The role of TBK1 and IKKe in the expression and activation of Pellino 1. Biochem J, 2011, 434(3): 537-548.
[4]. Clark K, MacKenzie KF, Petkevicius K, et al. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A, 2012, 109(42): 16986-16991.

Chemical Properties

StorageStore at -20°C
M.Wt464.6 (free-base)
Cas No.1190378-57-4 (free-base)
FormulaC26H36N6O2· xHCl
SynonymsMRT 67307;MRT-67307
Solubility≥23.25 mg/mL in DMSO, ≥30.67 mg/mL in EtOH, ≥52.5 mg/mL in H2O with gentle warming
SDFDownload SDF
Canonical SMILESO=C(C1CCC1)NCCCNC2=NC(NC3=CC(CN4CCOCC4)=CC=C3)=NC=C2C5CC5.[xHCl]
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

酶学实验 [1]:

激酶检测

底物和激酶用含有0.1% 2-mercaptoethanol、 0.1 毫摩尔 EGTA 以及 10 毫摩尔乙酸镁的50毫摩尔的Tris/HCl(pH 7.5)缓冲液稀释。加入[γ -32P]ATP使其终浓度为0.1毫摩尔来起始反应,并于30摄氏度孵育15分钟后通过加入SDS(1.0% (w/v))和EDTA(20 mM)来终止反应。100摄氏度加热5分钟后,磷酸化蛋白通过SDS/PAGE分离。

细胞实验 [1]:

细胞系

小鼠骨髓巨噬细胞

溶解方法

在DMSO中的溶解度> 23.3 mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0-10000 nM

应用

经MRT67307处理过的巨噬细胞能够增加由poly(I:C)以及 LPS诱导的p105和 RelA磷酸化,而且也能增强NF-κB的转录活性。此外, MRT67307能够抑制IFNβ合成以及IRF3磷酸化,而对NF-κB活化无影响,这表明MRT67307是通过抑制TBK1/IKKε激酶活性来达到阻断Pellino1的诱导。

References:

[1] Clark K, et al. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104.

生物活性

Description MRT67307是IKKe和TBK-1的双重抑制剂。
靶点 IKKe TBK-1        
IC50            

质量控制

化学结构

MRT67307 HCl