CHIR-090
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
CHIR-090是一种非常强效的、紧密结合的LpxC抑制剂,Ki值为4.0 nM [1]。
LpxC是一种锌依赖性酰胺酶,存在于几乎所有革兰氏阴性细菌中。LpxC是发展抗多重耐药性革兰氏阴性菌的新型抗生素物质的有希望的靶点[2]。
CHIR-090是一种强效的LpxC抑制剂,并具有与报道的LpxC抑制剂L-161不同的选择性。用大肠杆菌LpxC测试时,CHIR-090给药显示紧密结合抑制,Ki值为4.0 nM,Ki*=0.5 nM,K5=1.9/min 和K6=0.18/min [1]。在铜绿假单胞菌的细菌外排泵突变体中,CHIR-090治疗显示对MexAB-Oprm、MexCD-OprJ和MexEF-OprN的抑制功能[2]。低nM浓度的CHIR-090通过抑制LpxC同源基因,对大肠杆菌和绿脓杆菌都显示出显著的抗菌活性[3]。
在R.leguminosarum lpxC置换大肠杆菌lpxC的大肠杆菌W3110RL中,CHIR-090(1到10 μg/ml)治疗对在LB琼脂平板上的菌株生长没有影响,而在1 μg/ml 的CHIR-090存在时,野生型细胞约2小时后停止生长[1]。
参考文献:
[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.
- 1. Justin J. Zik, Sung Hwan Yoon, et al. "Caulobacter lipid A is conditionally dispensable in the absence of fur and in the presence of anionic sphingolipids." Cell Rep. 2022 May 31;39(9):110888. PMID: 35649364
- 2. Basta DW, Angeles-Albores D, et al. "Heat-shock proteases promote survival of Pseudomonas aeruginosa during growth arrest." Proc Natl Acad Sci U S A. 2020;117(8):4358–4367. PMID: 32029587
- 3. David W. Basta. "Genetic Determinants of Growth Arrest Survival in the Bacterial Pathogen Pseudomonas aeruginosa and the Role of Proteases." CALIFORNIA INSTITUTE OF TECHNOLOGY.2019.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 437.49 |
Cas No. | 728865-23-4 |
Formula | C24H27N3O5 |
Synonyms | CHIR 090;CHIR090 |
Solubility | ≥21.85 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | N-[(2S,3R)-3-hydroxy-1-(hydroxyamino)-1-oxobutan-2-yl]-4-[2-[4-(morpholin-4-ylmethyl)phenyl]ethynyl]benzamide |
SDF | Download SDF |
Canonical SMILES | CC(C(C(=O)NO)NC(=O)C1=CC=C(C=C1)C#CC2=CC=C(C=C2)CN3CCOCC3)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
Description | CHIR-090是一种强效的LpxC抑制剂。 | |||||
靶点 | LpxC | bacterial | ||||
IC50 |
质量控制和MSDS
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