5-hydroxy Diclofenac
(Synonyms: 5-羟基双氯芬酸) 目录号 : GC42546
An active metabolite of diclofenac
Cas No.:69002-84-2
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
5-hydroxy Diclofenac is a metabolite of the NSAID diclofenac formed by the cytochrome P450 (CYP) isoform CYP3A4. Diclofenac is a non-selective COX inhibitor. It inhibits human COX-1 and -2 with IC50 values of 0.9-2.7 and 1.5-20 µM, respectively. Diclofenac inhibits ovine COX-1 and -2 with IC50 values of 60 and 220 nM, respectively.
| Cas No. | 69002-84-2 | SDF | |
| 别名 | 5-羟基双氯芬酸 | ||
| Canonical SMILES | ClC1=C(NC2=C(CC(O)=O)C=C(O)C=C2)C(Cl)=CC=C1 | ||
| 分子式 | C14H11Cl2NO3 | 分子量 | 312.2 |
| 溶解度 | Soluble in DMSO | 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 | 3.2031 mL | 16.0154 mL | 32.0307 mL |
| 5 mM | 0.6406 mL | 3.2031 mL | 6.4061 mL |
| 10 mM | 0.3203 mL | 1.6015 mL | 3.2031 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。
Sono-activated persulfate oxidation of diclofenac: Degradation, kinetics, pathway and contribution of the different radicals involved
J Hazard Mater 2018 Sep 5;357:457-465.PMID:29935458DOI:10.1016/j.jhazmat.2018.06.031.
Degradation of a diclofenac aqueous solution was performed using persulfate anions activated by ultrasound. The objective of this study was to analyze different parameters affecting the diclofenac (DCF) removal reaction by the ultrasonic persulfate (US/PS) process and to evaluate the role played by various intermediate oxidative species such as hydroxyl- and sulfate radicals, superoxide radical anion or singlet oxygen in the removal process as well as to determine a possible reaction pathway. The effects of pH, initial persulfate anion concentration, ultrasonic amplitude and temperature on DCF degradation were examined. Sulfate and hydroxyl radicals were involved in the main reaction pathway of diclofenac. Diclofenac amide and three hydroxy-diclofenac isomers (3´-hydroxy diclofenac, 4´-hydroxy diclofenac and 5-hydroxy Diclofenac) were identified as reaction intermediates.
Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs
Biochemistry 1999 Oct 26;38(43):14264-70.PMID:10572000DOI:10.1021/bi991195u.
A comparison of the oxidations of diclofenac with microsomes of yeasts expressing various human liver cytochromes P450 showed that P450 2C9 regioselectively led to 4'-hydroxy diclofenac (4'-OHD) whereas P450 3A4 only led to 5-hydroxy Diclofenac (5-OHD). P450 2C19, 2C18, and 2C8 led to the simultaneous formation of 4'-OHD and 5-OHD (respective molar ratios of 1.3, 0.37, and 0.17), and P450 1A1, 1A2, 2D6, and 2E1 failed to give any detectable hydroxylated metabolite under identical conditions. P450 2C9 was found to be much more efficient for diclofenac hydroxylation than all the other P450s tested (k(cat)/K(M) of 1.6 min(-1) microM(-1) instead of 0.025 for the second more active P450), mainly because of markedly lower K(M) values (15 +/- 8 instead of values between 170 and 630 microM). Oxidation of diclofenac with chemical model systems of cytochrome P450 based on iron porphyrin catalysts exclusively led to the quinone imine derived from two-electron oxidation of 5-OHD, in an almost quantitative yield. Two derivatives of diclofenac lacking its COO(-) function were then synthesized; their oxidation by recombinant human P450 2Cs always led to a major product coming from their 5-hydroxylation. Substrate 2, which derives from reduction of the COO(-) function of diclofenac to the CH(2)OH function, was studied in more detail. All the P450s tested (1A1, 1A2, 2C8, 2C9, 2C18, 2C19, 2D6, and 3A4) almost exclusively led to its 5-hydroxylation. P450s of the 2C subfamily were found to be the most efficient catalysts for this reaction, with k(cat)/K(M) values between 0.2 and 1.6 min(-1) microM(-1). Oxidation of 2 with an iron porphyrin-based chemical model of cytochrome P450 also led to a product derived from the oxidation of 2 at position 5. These results show that oxidation of diclofenac and its derivative 2, either with chemical model systems of cytochrome P450 or with recombinant human P450s, generally occurs at position 5. This position, para to the NH group on the more electron-rich aromatic ring of diclofenac derivatives, is thus, as expected, the privileged site of reaction of electrophilic, oxidant species. The most spectacular exception to this chemoselective 5-oxidation of diclofenac derivatives was found for oxidation of diclofenac itself with P450 2C9 (and P450 2C19 and 2C18 to a lesser extent), which only led to 4'-OHD. A likely explanation for this result is a strict positioning of diclofenac in the P450 2C9 active site, via its COO(-) function, to completely orientate its hydroxylation toward position 4', which is not chemically preferred. P450 2C19, 2C18, and 2C8 would not lead to such a strict positioning as they give mixtures of 4'-OHD and 5-OHD. The above results show that diclofenac derivatives are interesting tools to compare the active site topologies of human P450 2Cs.
Input of selected human pharmaceutical metabolites into the Norwegian aquatic environment
J Environ Monit 2011 Feb;13(2):416-21.PMID:21152649DOI:10.1039/c0em00342e.
The occurrence of the metabolites of five human pharmaceuticals was investigated in treated wastewater, surface waters and sediments. Metabolites of carbamazepine (carbamazepine epoxide), diclofenac (4'- and 5-hydroxy Diclofenac) and atorvastatin (o- and p-hydroxy atorvastatin) were typically detected in flow proportional 24 h composite samples of wastewater effluent collected from the Norwegian cities of Oslo and Tromsø at higher concentrations than the parent pharmaceutical. The concentrations determined in discharged effluent were as high as 3700 ng L(-1) for 5-hydroxy Diclofenac. The overall mean concentration of metabolites being typically higher in the primary treated effluent from the city of Tromsø compared to the tertiary treatment performed on the Oslo effluent. Metabolites of carbamazepine (carbamazepine-10,11-epoxide), metoprolol (α-hydroxy metoprolol) and simvastatin (hydroxy simvastatin) were detected in surface water samples collected from Oslofjord at concentrations of up to 108 ng L(-1), whilst α-hydroxy metoprolol and simvastatin hydroxy carboxylic acid were also detected in sediments at low ng L(-1) concentrations. These screening data show that the metabolites of selected pharmaceuticals are being discharged into the Norwegian coastal environment and that certain metabolites occur in marine surface waters and sediments.
Occurrence of diclofenac and selected metabolites in sewage effluents
Sci Total Environ 2008 Nov 1;405(1-3):310-6.PMID:18640705DOI:10.1016/j.scitotenv.2008.05.036.
Many pharmaceuticals along with their metabolites have been detected in environmental water samples in the recent decades. The analgesic diclofenac is widely used and thus enters the aquatic environment. Already at realistic environmental concentration levels harmful effects to different organisms have been demonstrated. As this could also be expected for its metabolites, their fate was examined. Six wastewater treatment plant effluents collected throughout Germany were analyzed for the drug and two of its hydroxylated metabolites, 4'-hydroxy diclofenac (4'-OHD) and 5-hydroxy Diclofenac (5-OHD), together with the lactam of 4'-OHD, 4'-hydroxy diclofenac dehydrate (4'-OHDD). A quantitative analytical method has been developed using solid-phase extraction followed by LC-ESI-MS/MS. The limits of quantitation (LOQ) in sewage effluent were 0.06 mug/l for diclofenac and its hydroxyl metabolites and 0.07 microg/l for 4'-OHDD. Recoveries ranged from 62 to 81%. The metabolites were detected in the samples in median concentration ranges of
Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria: Possible role in drug induced liver injury (DILI)
Toxicol In Vitro 2016 Mar;31:93-102.PMID:26627130DOI:10.1016/j.tiv.2015.11.020.
Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy Diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism based inhibition of ATP synthesis is exerted by diclofenac and its metabolites. Phase-I metabolite (4'-OH-Dic) and Phase-II metabolites (DicGluA and DicSG) showed potent inhibition (2-5 fold) of ATP synthesis, where as 5-OH-Dic, one of the Phase-I metabolite, was a less potent inhibitor as compared to Dic. The calculated kinetic constants of mechanism based inhibition of ATP synthesis by Dic showed maximal rate of inactivation (Kinact) of 2.64 ± 0.15 min(-1) and half maximal rate of inactivation (KI) of 7.69 ± 2.48 μM with Kinact/KI ratio of 0.343 min(-1) μM(-1). Co-incubation of mitochondria with Dic and reduced GSH exhibited a protective effect on Dic mediated inhibition of ATP synthesis. Our data from this study strongly indicate that Dic as well as its metabolites could be involved in the hepato-toxic action through inhibition of ATP synthesis.