PHOP
(Synonyms: CAY10402, Phenyl hexanoyl oxazolopyridine) 目录号 : GC40955
An exceptionally potent FAAH inhibitor
Cas No.:288862-83-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fatty acid amide hydrolase (FAAH) is the enzyme responsible for hydrolysis and inactivation of fatty acid amides including anandamide and oleamide. PHOP is a potent FAAH inhibitor, exhibiting Ki values of 0.094 nM and 0.2 nM for the human and rat enzymes, respectively. Using a proteomics approach, PHOP was screened against the serine hydrolase family of enzymes, of which FAAH is a member. In this assay, PHOP exhibited IC50 values of 1.1 nM, 1.4 nM, and >100 µM for FAAH, triacylglycerol hydrolase (TGH), and an uncharacterized hydrolase (KIAA1363), respectively. Knowledge of the specificity of PHOP obtained from this experiment should allow for more accurate interpretation of results using this inhibitor in complex environments such as whole cells or animals.
| Cas No. | 288862-83-9 | SDF | |
| 别名 | CAY10402, Phenyl hexanoyl oxazolopyridine | ||
| Canonical SMILES | O=C(CCCCCc1ccccc1)c1nc2ncccc2o1 | ||
| 分子式 | C18H18N2O2 | 分子量 | 294.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2)(1:2): .25 mg/ml,Ethanol: 10 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3967 mL | 16.9837 mL | 33.9674 mL |
| 5 mM | 0.6793 mL | 3.3967 mL | 6.7935 mL |
| 10 mM | 0.3397 mL | 1.6984 mL | 3.3967 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
How the PHOP/PhoQ System Controls Virulence and Mg2+ Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution
Microbiol Mol Biol Rev 2021 Aug 18;85(3):e0017620.PMID:34191587DOI:10.1128/MMBR.00176-20.
The PHOP/PhoQ two-component system governs virulence, Mg2+ homeostasis, and resistance to a variety of antimicrobial agents, including acidic pH and cationic antimicrobial peptides, in several Gram-negative bacterial species. Best understood in Salmonella enterica serovar Typhimurium, the PHOP/PhoQ system consists o-regulated gene products alter PhoP-P amounts, even under constant inducing conditions. PhoP-P controls the abundance of hundreds of proteins both directly, by having transcriptional effects on the corresponding genes, and indirectly, by modifying the abundance, activity, or stability of other transcription factors, regulatory RNAs, protease regulators, and metabolites. The investigation of PHOP/PhoQ has uncovered novel forms of signal transduction and the physiological consequences of regulon evolution.
[Mycobacterium tuberculosis PHOP system]
Wei Sheng Wu Xue Bao 2017 Apr 4;57(4):461-7.PMID:29756729doi
PhoPR is an important two-component regulatory system in Mycobacterium tuberculosis. PHOP is essential for virulence as a response regulator involved in cell wall lipid biosynthesis and regulation of gene expression. In this review, the structure, function and vaccine application of PHOP were summarized, as well as some questions that need to be solved.
Methylation of PHOP by CheR Regulates Salmonella Virulence
mBio 2021 Oct 26;12(5):e0209921.PMID:34544273DOI:10.1128/mBio.02099-21.
The two-component system PHOP/PhoQ is essential for Salmonella enterica serovar Typhimurium virulence. Here, we report that PHOP is methylated extensively. Two consecutive glutamate (E) and aspartate (D)/E residues, i.e., E8/D9 and E107/E108, and arginine (R) 112 can be methylated. Individual mutation of these above-mentioned residues caused impaired phosphorylation and dimerization or DNA-binding ability of PHOP to a different extent and led to attenuated bacterial virulence. With the help of specific antibodies recognizing methylated E8 and monomethylated R112, we found that the methylation levels of E8 or R112 decreased dramatically when bacteria encountered low magnesium, acidic pH, or phagocytosis by macrophages, under which PHOP can be activated. Furthermore, CheR, a bacterial chemotaxis methyltransferase, was identified to methylate R112. Overexpression of cheR decreased PHOP activity but increased PHOP stability. Together, the current study reveals that methylation plays an important role in regulating PHOP activities in response to environmental cues and, consequently, modulates Salmonella virulence. IMPORTANCE Posttranslational modifications (PTMs) play an important role in regulating enzyme activities, protein-protein interactions, or DNA-protein recognition and, consequently, modulate many biological functions. We demonstrated that PHOP, the response regulator of PHOP/PhoQ two-component system, could be methylated on several evolutionally conserved amino acid residues. These amino acid residues were crucial for PHOP phosphorylation or dimerization, DNA-binding ability of PHOP, and Salmonella virulence. Interestingly, methylation negatively regulated the activity of PHOP. A bacterial chemotaxis methyltransferase CheR was involved in PHOP methylation. Methylation of PHOP could stabilize it in an inactive conformation. Our work provides a more informative depiction of PHOP PTM and markedly improves our understanding of the coordinate regulation of bacterial chemotaxis and virulence.
PHOP induces RyjB expression under acid stress in Escherichia coli
J Biochem 2022 Mar 3;171(3):277-285.PMID:34967409DOI:10.1093/jb/mvab142.
Bacterial small RNAs (sRNAs) play a pivotal role in post-transcriptional regulation of gene expression and participate in many physiological circuits. An ~80-nt-long RyjB was earlier identified as a novel sRNA, which appeared to be accumulated in all phases of growth in Escherichia coli. We have taken a comprehensive approach in the current study to understand the regulation of ryjB expression under normal and pH stress conditions. RpoS was not necessary for ryjB expression neither at normal condition nor under acid stress. Hfq also emerged to be unnecessary for RyjB accumulation. Interestingly, RyjB was detected as a novel acid stress induced sRNA. A DNA binding protein PHOP, a component of PHOP/Q regulon, was found to regulate ryjB expression at low pH, as the elimination of PHOP allele in the chromosome exhibited a basal level of RyjB expression under acid stress. Ectopic expression of PHOP in ΔPHOP cells restored the overabundance of RyjB in the cell. Overexpression of RyjB increased the abundance of sgcA transcripts, with which RyjB shares a 4-nt overlap. The current study increases our knowledge substantially regarding the regulation of ryjB expression in E. coli cell.
PHOP/PhoQ: macrophage-specific modulators of Salmonella virulence?
Mol Microbiol 1991 Sep;5(9):2073-8.PMID:1766380DOI:10.1111/j.1365-2958.1991.tb02135.x.
The regulation of gene expression by the two-component regulatory system PHOP/PhoQ is necessary for Salmonella typhimurium survival within macrophages, defensin resistance, acid resistance, and murine typhoid fever pathogenesis. Salmonella experience multiple environments during mammalian infection and survival requires tightly regulated gene expression. After phagocytosis by macrophages, signal transduction by PhoQ results in the transcription of phoP-activated genes (pags) encoding proteins essential to bacterial survival and virulence. One such gene, pagC, encodes an envelope protein with amino acid similarity to an epithelial cell invasion protein of Yersina enterocolitica, Ail, and a bacteriophage lambda outer membrane protein, Lom. The PHOP and PhoQ proteins can also repress the synthesis of proteins, encoded by PHOP repressed genes (prgs), when pags are maximally expressed. If prgs encode receptors for toxic compounds, prg repression may protect the cell within macrophages when pag expression is most necessary. At least one prg locus, prgH, is required for full S. typhimurium mouse virulence. Within the macrophage, different environments may stimulate a switch from pag to prg expression that is necessary to Salmonella survival. prg expression may also be necessary for surviving nonmacrophage environments. Study of the PHOP regulon should lead to the discovery of new virulence factors, increase knowledge of how gene regulation is essential to bacterial virulence, and perhaps lead to the development of better vaccines for typhoid fever.