N-Cyclohexanecarbonylpentadecylamine
目录号 : GC44339A selective acidic PEAase inhibitor
Cas No.:702638-84-4
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
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Numerous analogs of fatty acyl ethanolamides potentiate the intrinsic biological activity of endocannabinoids. This potentiation is ascribed either to inhibition of AEA reuptake into neurons, or inhibition of fatty acid amide hydrolase (FAAH) within the neurons. However, Ueda has recently cloned another amidase, the acidic palmitoyl ethanolamidase (PEAase) that promotes the hydrolysis of palmitoylethanolamide. N-Cyclohexanecarbonylpentadecylamine is a selective inhibitor of acidic PEAase, inhibiting the enzyme with an IC50 of 4.5 µM, while failing to inhibit FAAH even at 100 µM.
Cas No. | 702638-84-4 | SDF | |
Canonical SMILES | CCCCCCCCCCCCCCCNC(=O)C1CCCCC1 | ||
分子式 | C22H43NO | 分子量 | 337.6 |
溶解度 | Ethanol: 2 mg/ml | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.9621 mL | 14.8104 mL | 29.6209 mL |
5 mM | 0.5924 mL | 2.9621 mL | 5.9242 mL |
10 mM | 0.2962 mL | 1.481 mL | 2.9621 mL |
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2.
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N-Cyclohexanecarbonylpentadecylamine: a selective inhibitor of the acid amidase hydrolysing N-acylethanolamines, as a tool to distinguish acid amidase from fatty acid amide hydrolase
Biochem J 2004 Apr 1;379(Pt 1):99-106.PMID:14686878DOI:10.1042/BJ20031695.
Anandamide ( N-arachidonoylethanolamine) and other bioactive N-acylethanolamines are degraded to their corresponding fatty acids and ethanolamine. This hydrolysis is mostly attributed to catalysis by FAAH (fatty acid amide hydrolase), which exhibits an alkaline pH optimum. In addition, we have identified another amidase which catalyses the same reaction exclusively at acidic pH values [Ueda, Yamanaka and Yamamoto (2001) J. Biol. Chem. 276, 35552-35557]. In attempts to find selective inhibitors of this acid amidase, we screened various derivatives of palmitic acid, 1-hexadecanol, and 1-pentadecylamine with N-palmitoylethanolamine as substrate. Here we show that N-Cyclohexanecarbonylpentadecylamine inhibits the acid amidase from rat lung with an IC50 of 4.5 microM, without inhibiting FAAH at concentrations up to 100 microM. The inhibition was reversible and non-competitive. This compound also inhibited the acid amidase in intact alveolar macrophages. With the aid of this inhibitor, it was revealed that rat basophilic leukaemia cells possess the acid amidase as well as FAAH. Thus the inhibitor may be a useful tool to distinguish the acid amidase from FAAH in various tissues and cells and to elucidate the physiological role of the enzyme.
A second N-acylethanolamine hydrolase in mammalian tissues
Neuropharmacology 2005 Jun;48(8):1079-85.PMID:15910884DOI:10.1016/j.neuropharm.2004.12.017.
It is widely accepted that fatty acid amide hydrolase (FAAH) plays a central role in the hydrolysis of anandamide. However, we found a second N-acylethanolamine hydrolase in animal tissues which hydrolyzed anandamide at acidic pH. This "acid amidase" was first detected with the particulate fraction of human megakaryoblastic CMK cells, and was solubilized by freezing and thawing without detergent. The enzyme was distinguishable from FAAH in terms of (1) the optimal activity at pH 5, (2) stimulation by dithiothreitol, (3) low sensitivity to two FAAH inhibitors (methyl arachidonyl fluorophosphonate and phenylmethylsulfonyl fluoride), and (4) high content in lung, spleen and macrophages of rat. The acid amidase purified from rat lung was the most active with N-palmitoylethanolamine among various long-chain N-acylethanolamines. To develop specific inhibitors for this enzyme, we screened various analogues of N-palmitoylethanolamine. Among the tested compounds, N-Cyclohexanecarbonylpentadecylamine was the most potent inhibitor which does-dependently inhibited the enzyme with an IC(50) value of 4.5 microM without inhibiting FAAH at concentrations up to 100 microM. The inhibitor was a useful tool to distinguish the acid amidase from FAAH with rat basophilic leukemia (RBL-1) cells that express both the enzymes.
Involvement of N-acylethanolamine-hydrolyzing acid amidase in the degradation of anandamide and other N-acylethanolamines in macrophages
Biochim Biophys Acta 2005 Oct 1;1736(3):211-20.PMID:16154384DOI:10.1016/j.bbalip.2005.08.010.
Bioactive N-acylethanolamines including the endocannabinoid anandamide are known to be hydrolyzed to fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH). In addition, we recently cloned an isozyme termed "N-acylethanolamine-hydrolyzing acid amidase (NAAA)", which is active only at acidic pH [Tsuboi, Sun, Okamoto, Araki, Tonai, Ueda, J. Biol. Chem. 285 (2005) 11082-11092]. However, physiological roles of NAAA remained unclear. Here, we examined a possible contribution of NAAA to the degradation of various N-acylethanolamines in macrophage cells. NAAA mRNA as well as FAAH mRNA was detected in several macrophage-like cells, including RAW264.7, and mouse peritoneal macrophages. The homogenates of RAW264.7 cells showed both the NAAA and FAAH activities which were confirmed with the aid of their respective specific inhibitors, N-Cyclohexanecarbonylpentadecylamine (CCP) and URB597. As analyzed with intact cells, RAW264.7 cells and peritoneal macrophages degraded anandamide, N-palmitoylethanolamine, N-oleoylethanolamine, and N-stearoylethanolamine. Pretreatment of the cells with CCP or URB597 partially inhibited the degradation, and a combination of the two compounds caused more profound inhibition. In contrast, the anandamide hydrolysis in mouse brain appeared to be principally attributable to FAAH despite the expression of NAAA in the brain. These results suggested that NAAA and FAAH cooperatively degraded various N-acylethanolamines in macrophages.
A new mass spectrometry based bioassay for the direct assessment of hyaluronidase activity and inhibition
J Microbiol Methods 2015 Dec;119:163-7.PMID:26519769DOI:10.1016/j.mimet.2015.10.019.
The development of drug resistance by bacterial pathogens is a growing threat. Drug resistant infections have high morbidity and mortality rates, and treatment of these infections is a major burden on the health care system. One potential strategy to prevent the development of drug resistance would be the application of therapeutic strategies that target bacterial virulence. Hyaluronidase is virulence factor that plays a role in the ability of Gram-positive bacteria such as Staphyloccus aureus and Streptococcus agalactiae to spread in tissue. As such, this enzyme could be a target for the development of future anti-virulence therapies. To facilitate the identification of hyaluronidase inhibitors, quantitative and reproducible assays of hyaluronidase activity are required. In the present study, we developed a new mass spectrometry based bioassay for this purpose. This assay directly measures the quantity of a degradation product (3-(4-deoxy-β-D-gluc-4-enuronosyl)-N-acetyl-D-glucosamine) produced by the hyaluronidase enzyme. Validation parameters for the new assay are as follows: repeatability, <7%; intermediate precision, <10%; range, 0.78-50 μM; limit of detection, 0.29 μM; and limit of quantification, 0.78 μM. Using the new assay, the IC50 value for a published inhibitor of S. agalactiae hyaluronidase, ascorbic acyl 6-palmitate, was 8.0±1.0 μM. We also identified a new hyaluronidase inhibitor, N-Cyclohexanecarbonylpentadecylamine, with an IC50 of 30.4±9.8 μM. In conclusion, we describe a new, direct, and reproducible method for assessing hyaluronidase activity using mass spectrometry that can facilitate the discovery of inhibitors.