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SA72 Sale

目录号 : GC31239

SA72是高度选择性的脂肪酸酰胺水解酶(FAAH)抑制剂。

SA72 Chemical Structure

Cas No.:934809-60-6

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1mg
¥11,424.00
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5mg
¥22,848.00
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10mg
¥38,824.00
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20mg
¥68,544.00
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Sample solution is provided at 25 µL, 10mM.

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实验参考方法

Kinase experiment:

Rat liver microsomes and cytosol are as sources of carboxylesterase to screen activity. Assays are conducted in 96-well microtiter plates at room temperature. Briefly, 0.5 mg liver microsomes or 2 mg cytosol are incubated with 10 mM SA72 for 30 min and then substrate p-nitrophenyl acetate is added to a final concentration of 1 mM. The plate is read 10 min after substrate addition at 405 nm for the appearance of the p-nitrophenol. The carboxylesterase activities in liver extracts without inhibitor added are set at 100% and the remaining carboxylesterase activities after incubation with inhibitors are calculated relative to the control[1].

References:

[1]. Zhang D, et al. Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets. Neuropharmacology. 2007 Mar;52(4):1095-105.

产品描述

SA72 is a highly selective fatty acid amide hydrolase (FAAH) inhibitor.

Fatty acid amide hydrolase (FAAH) is the primary regulator of several bioactive lipid amides including anandamide. Inhibitors of FAAH are potentially useful for the treatment of pain, anxiety, depression, and other nervous system disorders. However, FAAH inhibitors must display selectivity for this enzyme relative to the numerous other serine hydrolases present in the human proteome in order to be therapeutically acceptable. SA-72 is also a carbamate inhibitor. However, SA-72 shows exceptional selectivity for FAAH. Tested carboxylesterases are not off-targets for SA-72. SA-72 does not have major effects on the level of carboxylesterase activities in liver microsomes[1].

[1]. Zhang D, et al. Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets. Neuropharmacology. 2007 Mar;52(4):1095-105.

Chemical Properties

Cas No. 934809-60-6 SDF
Canonical SMILES O=C(OCC(N)=O)NCCCC1OCC(C2=C3C=CC(OC)=CC3=CC=C2)CO1
分子式 C21H26N2O6 分子量 402.44
溶解度 Soluble in DMSO 储存条件 Store at -20°C
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溶解性数据

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1 mg 5 mg 10 mg
1 mM 2.4848 mL 12.4242 mL 24.8484 mL
5 mM 0.497 mL 2.4848 mL 4.9697 mL
10 mM 0.2485 mL 1.2424 mL 2.4848 mL
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Research Update

Effect of space allowance and mixing on growth performance and body lesions of grower-finisher pigs in pens with a single wet-dry feeder

Background: Low space allowance (SA) and mixing may result in reduced growth performance (GP) and animal welfare issues because of adverse social behaviours directed to pen mates. This could be exacerbated in pens with single space feeders owing to social facilitation of feeding behaviour. The present study aimed to investigate the effect of SA and mixing on GP and body lesions (BL) in pens with one single space wet-dry feeder. Results: Two experiments were conducted on grower-finisher pigs from 10 to 21 weeks of age. In Exp1, pigs (N = 216) were assigned to three SA; 0.96 m2/pig (n = 6 pens; 10 pigs/pen; SA96), 0.84 m2/pig (n = 6; 12 pigs/pen; SA84) and 0.72 m2/pig (n = 6; 14 pigs/pen; SA72), in a randomized design. In Exp2, pigs (N = 230) were used in a 2 × 2 factorial randomized design considering SA and mixing as treatments. Pigs were assigned to two SA; 0.96 m2/pig (n = 10 pens; 10 pigs/pen; SA96) and 0.78 m2/pig (n = 10; 13 pigs/pen; SA78) and were either mixed or not at the entry to the finishing facility. GP was not affected by SA (P > 0.05) in either experiment. In Exp2, non-mixed pigs were 5.4 kg heavier (P < 0.001), gained 74 g more per day (P = 0.004), consumed 101.8 g more of feed per day (P = 0.007) and tended to have higher feed efficiency (P = 0.079) than mixed pigs from 11 to 21 weeks of age. Number of BL was affected by SA in both experiments. In Exp1, SA72 pigs had 74.4 and 97.4% more BL than SA96 and SA84 pigs at 20 weeks of age respectively (P < 0.01). In Exp2, SA78 pigs had 48.6, 43.6 and 101.3% more BL than SA96 pigs at 12, 16 and 21 weeks of age respectively (P < 0.05). Mixing did not affect the number of BL from 12 to 21 weeks of age in Exp2 (P > 0.05). Conclusion: Mixing had a considerable effect on growth performance thus, strategies to avoid or mitigate mixing should be considered. Although space allowance had no effect on growth performance, high number of body lesions in the lower space allowance indicates that space allowances equal or below 0.78 m2/pig are detrimental to the welfare of pigs despite following the EU legislation.

Curtobacterium ammoniigenes sp. nov., an ammonia-producing bacterium isolated from plants inhabiting acidic swamps in actual acid sulfate soil areas of Vietnam

The ammonia-producing bacteria B55(T), CA73, SA69 and SA72 were isolated from the waterweeds Ludwigia adscendens (B55(T)) and Eleocharis dulcis (CA73, SA69 and SA72) grown in highly acidic swamps (pH 2-4) in actual acid sulfate soil areas of Vietnam. The isolates were Gram-positive, irregular rod-shaped, non-spore-forming bacteria. On the basis of 16S rRNA gene sequence similarity, strain B55(T) was shown to belong to the genus Curtobacterium of the class Actinobacteria. Chemotaxonomic data (MK-9 as major isoprenoid quinone, d-ornithine as cell-wall diamino acid, acetyl as the acyl type of peptidoglycan) supported the affiliation of all four strains to this genus. Although their 16S rRNA gene sequence similarity was 99 % to species with validly published names within the genus, they formed a group that was distinct in the phylogenetic tree, and DNA-DNA relatedness values to these established species were less than 10 %. The results of physiological and biochemical tests and major fatty acids (cyclohexyl-C(17 : 0), anteiso-C(17 : 0) and cyclohexyl-C(19 : 0)) allowed phenotypic differentiation of these strains from the species of Curtobacterium with validly published names. Therefore, strains B55(T), CA73, SA69 and SA72 represent a novel species, for which the name Curtobacterium ammoniigenes sp. nov. is proposed. The type strain is B55(T) (=NBRC 101786(T)=VTCC D6-11(T)=JCM 14609(T)).

Subchronic feeding, allergenicity, and genotoxicity safety evaluations of single strain bacterial protein

Microbial proteins are potentially important alternatives to animal protein. A safety assessment was conducted on a Clostridium protein which can serve as a high-quality protein source in human food. A battery of toxicity studies was conducted comprising a 14-day dose-range finding dietary study in rats, 90-day dietary study in rats and in vitro genotoxicity studies. The allergenic potential was investigated by bioinformatics analysis. In the 90-day feeding study, rats were fed diets containing 0, 5.0, 7.5, and 10% Clostridium protein. The Clostridium protein-containing diets were well-tolerated and no adverse effects on the health or growth were observed. Significant reductions in neutrophil counts were observed in all female rats compared to controls, which were slightly outside of reference ranges. These effects were not deemed to be adverse due to the absence of comparable findings in male rats and high physiological variability of measured values within groups. A No-Observed-Adverse-Effect-Level (NOAEL) of at least 10% Clostridium protein, the highest dose tested and corresponding to 5,558 and 6,671 mg/kg body weight/day for male and female rats, respectively, was established. No evidence of genotoxicity was observed and the allergenic potential was low. These results support the use of Clostridium protein as a food ingredient.

Oral health in Alzheimer's disease: a multicenter case-control study

Objectives: The aim of this case-control study was to carry out an oral health assessment on a group of Alzheimer's patients and to establish a hypothesis regarding the implication of the characteristics of the disease and the treatment of oral health.
Materials and methods: A total of 70 Alzheimer's patients, residents at the Alzheimer Center Reina Sofia Foundation (Madrid, Spain) and at the Alzheimer State Reference Center (Salamanca, Spain), and 36 controls (companions/acquaintances), were studied by oral examination and saliva sampling. The oral health indices DMFT/DMFS, CPI, the prosthetic condition, oral hygiene, saliva volume, and pH, as well as the specific microbiological parameters governing the risk of developing caries were assessed.
Results: Alzheimer's patients exhibited, as compared to the control group, (1) fewer teeth (10.9 ± 10.5 vs 23.7 ± 6.5), (2) fewer obturations (2.2 ± 3.4 vs 6.6 ± 5.6), (3) fewer periodontally healthy sextants (0.1 ± 0.4 vs 1.4 ± 2.2), (4) worse oral hygiene (43.1 vs 72.2% brushed), (5) greater use of removable prostheses (47.8 vs 8.4%), (6) higher incidence of candida infection (11.8 vs 0.0%) and cheilitis (15.9 vs 0.0%), (7) lower salivary flow (0.6 ± 0.6 vs 1.1 ± 0.6), and (8) lower buffering capacity (46 vs 80%).
Conclusions: After taking into account the influence of age, Alzheimer's patients had worse oral health (caries and periodontal disease), more mucosal lesions (cheilitis and candidiasis), and worse saliva quantity and quality.
Clinical relevance: Clinicians should be aware of the implications of Alzheimer's disease in oral health, in order to stablish the effective preventive measures and the optimal treatment plan.

Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit multiple carboxylesterases as off-targets

Fatty acid amide hydrolase (FAAH) is the primary regulator of several bioactive lipid amides including anandamide. Inhibitors of FAAH are potentially useful for the treatment of pain, anxiety, depression, and other nervous system disorders. However, FAAH inhibitors must display selectivity for this enzyme relative to the numerous other serine hydrolases present in the human proteome in order to be therapeutically acceptable. Here we employed activity-based protein profiling (ABPP) to assess the selectivity of FAAH inhibitors in multiple rat and human tissues. We discovered that some inhibitors, including carbamate compounds SA-47 and SA-72, and AM404 are exceptionally selective while others, like URB597, BMS-1, OL-135, and LY2077855 are less selective, displaying multiple off-targets. Since proteins around 60kDa constitute the major off-targets for URB597 and several other FAAH inhibitors with different chemical structures, we employed the multi-dimensional protein identification technology (MudPIT) approach to analyze their identities. We identified multiple carboxylesterase isozymes as bona fide off-targets of FAAH inhibitors. Consistently, enzymatic assay confirmed inhibition of carboxylesterase activities in rat liver by FAAH inhibitors. Since carboxylesterases hydrolyze a variety of ester-containing drugs and prodrugs, we speculate that certain FAAH inhibitors, by inhibiting carboxylesterases, might have drug-drug interactions with other medicines if developed as therapeutic agents.