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CHIR-090

现货
Catalog No.
A3307
LpxC抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,750.00
现货
5mg
¥ 1,760.00
现货
10mg
¥ 2,860.00
现货
50mg
¥ 9,920.00
现货
200mg
¥ 22,990.00
现货

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Background

CHIR-090 is a very potent, low, tight-binding inhibitor of LpxC with Ki value of 4.0 nM [1].
LpxC is a zinc-dependent amidase and present in almost all Gram-negative bacteria. LpxC is a promising target for the development of novel antibiotic substances against multigrug-resistant Gram-negative bacteria [2].
CHIR-090 is a potent LpxC inhibitor and has a different selectivity with the reported LpxC inhibitor L-161. When tested with Escherichia coli LpxC, administration of CHIR-090 showed tight inhibition with Ki value of 4.0 nM, Ki*=0.5 nM, K5=1.9/min and K6=0.18/min [1]. In bacterial P.aeruginosa efflux pupm mutants, CHIR-090 treatment showed inhibition function on MexAB-Oprm, MexCD-OprJ and MexEF-OprN [2]. CHIR-090 showed remarkable antibiotic activity against both E.coli and P.aeruginosa by inhibiting LpxC orthologs at low nM concentrations [3].
In E.coli W3110RL with R.legumunosarum lpxC replacement of E.coli lpxC, CHIR-090 (1 to 10 μg/ml) treatment had no effect on strain growth on LB agar plates while wild-type cells stopped growing after about 2 h in the presence of 1 μg/ml CHIR-090 [1].
References:
[1].Barb, A.W., et al., Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli. Biochemistry, 2007. 46(12): p. 3793-802.
[2].Barb, A.W. and P. Zhou, Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis. Curr Pharm Biotechnol, 2008. 9(1): p. 9-15.
[3].McClerren, A.L., et al., A slow, tight-binding inhibitor of the zinc-dependent deacetylase LpxC of lipid A biosynthesis with antibiotic activity comparable to ciprofloxacin. Biochemistry, 2005. 44(50): p. 16574-83.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt437.49
Cas No.728865-23-4
FormulaC24H27N3O5
SynonymsCHIR 090;CHIR090
Solubility≥21.85 mg/mL in DMSO, <2.27 mg/mL in EtOH, <2.42 mg/mL in H2O
Chemical NameN-[(2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl]-4-[2-[4-(morpholin-4-ylmethyl)phenyl]ethynyl]benzamide
SDFDownload SDF
Canonical SMILESCC(C(C(=O)NO)NC(=O)C1=CC=C(C=C1)C#CC2=CC=C(C=C2)CN3CCOCC3)O
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]:

LpxC 活性实验

UDP-3-O-(R-3-羟基肉豆蔻酰)-N-乙酰氨基葡萄糖和[α-32P] UDP-3-O-(R-3-羟基肉豆蔻酰)-N-乙酰葡糖胺如前所述酶促制备。 使用5μM底物进行LpxC活性测定,除非另有说明;另外,将10%DMSO加入到测定混合物中,并在加入抑制剂(溶解于DMSO中)时保持恒定。除非另有说明,酶的浓度比抑制剂或底物的浓度少至少10倍。当在测定之前与抑制剂预孵育时,将酶在含有1mg / mL BSA和10%DMSO的25mM磷酸钠(pH 7.4)中稀释。将预孵育混合物保持在冰上15分钟,然后将酶按1:4稀释加入测定混合物起始反应。初始速度由反应进程曲线的线性部分计算(<10%底物转化为产物)。

细胞实验[1]:

细胞系

野生型大肠杆菌W3110和大肠杆菌W3110RL

溶解方法

该化合物在DMSO中的溶解度>21.9mg/mL。为了获得更高的浓度,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

1 μg/mL

应用

在1μg/ mL CHIR-090存在下,野生型大肠杆菌W3110在约2小时后停止生长。豆科植物lpxC替代大肠杆菌lpxC的染色体拷贝的大肠杆菌W3110RL对CHIR-090具有抗性。液体培养基中CHIR-090对W3110RL的MIC为100μg/ mL,而W3110为0.25μg/ mL。

References:

[1].Barb, A.W., et al., Inhibition of lipid A biosynthesis as the primary mechanism of CHIR-090 antibiotic activity in Escherichia coli. Biochemistry, 2007. 46(12): p. 3793-802.

生物活性

Description CHIR-090是一种强效的LpxC抑制剂。
靶点 LpxC bacterial        
IC50            

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