6-Hydroxymelatonin
(Synonyms: 苏达灭) 目录号 : GC33704
An active metabolite of melatonin
Cas No.:2208-41-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
6-hydroxy Melatonin is an active metabolite of melatonin .1,2,3,4,5 It is formed from melatonin by the cytochrome P450 (CYP) isoform CYP1A2 in human liver microsomes.6 6-hydroxy Melatonin is a melatonin 1A (MT1A), MT1B, and MT2 receptor agonist.1,2 It inhibits dopamine release from isolated rabbit retina (IC50 = 0.0016 ?M).3 6-hydroxy Melatonin (10 and 100 ?M) reduces increases in the levels of NF-κB, IL-6, and IL-8 and decreases in glutathione (GSH) levels in LPS- and peptidoglycan G-stimulated human umbilical vein endothelial cells (HUVECs) in an in vitro model of sepsis.4 It reduces iron-induced lipid oxidation in rat hippocampal homogenate when administered at a dose of 10 mg/kg.5
1.Dubocovich, M.L., Masana, M.I., Iacob, S., et al.Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptorNaunyn-Schmiedeberg's Arch. Pharmacol.355(3)365-375(1997) 2.Dubocovich, M.L.Melatonin receptors: Are there multiple subtypes?Trends Pharamacol. Sci.16(2)50-56(1995) 3.Dubocovich, M.L.Characterization of a retinal melatonin receptorJ. Pharmacol. Exp. Ther.234(2)395-401(1985) 4.Lowes, D.A., Almawash, A.M., Webster, N.R., et al.Melatonin and structurally similar compounds have differing effects on inflammation and mitochondrial function in endothelial cells under conditions mimicking sepsisBr. J. Anaesth.107(2)193-201(2011) 5.Maharaj, D.S., Maharaj, H., Daya, S., et al.Melatonin and 6-hydroxymelatonin protect against iron-induced neurotoxicityJ. Neurochem.96(1)78-81(2006) 6.H?rtter, S., Wang, X., Weigmann, H., et al.Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatoninJ. Clin. Psychopharmacol.21(2)167-174(2001)
| Cas No. | 2208-41-5 | SDF | |
| 别名 | 苏达灭 | ||
| Canonical SMILES | CC(NCCC1=CNC2=C1C=C(OC)C(O)=C2)=O | ||
| 分子式 | C13H16N2O3 | 分子量 | 248.28 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml,Ethanol: 20 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 4.0277 mL | 20.1386 mL | 40.2771 mL |
| 5 mM | 0.8055 mL | 4.0277 mL | 8.0554 mL |
| 10 mM | 0.4028 mL | 2.0139 mL | 4.0277 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。
Development and Validation of an LC-MS/MS-Based Method for Quantifying Urinary Endogenous 6-Hydroxymelatonin
Chem Pharm Bull (Tokyo) 2022;70(5):375-382.PMID:35491194DOI:10.1248/cpb.c21-00982.
Evaluation of endogenous melatonin (MEL) secretion using its urinary metabolites is useful for the treatment of circadian rhythm sleep disorders. The primary melatonin metabolites excreted in the urine are 6-Hydroxymelatonin (6-O-MEL) sulfate (S-O-MEL) and 6-O-MEL glucuronate, which result from sequential MEL metabolism by phases I and II drug metabolizing enzymes. To determine the accurate MEL secretion level, these urinary metabolites should be enzymatically deconjugated and converted into MEL. Furthermore, the use of LC-tandem mass spectrometry (LC-MS/MS) is preferable for the precision of this determination. Therefore, as part of our ongoing efforts to ultimately determine the level of MEL secretion, we herein aimed to develop an LC-MS/MS-based quantification method for 6-O-MEL and optimize deconjugation conditions. We determined the LC-MS/MS conditions of 6-O-MEL measurement and optimized the conditions of enzymatic reactions. The most efficient S-O-MEL deconjugation (102.1%) was achieved with Roche Glucuronidase/Arylsulfatase (from Helix pomatia) at 37 °C, pH-4.0 reaction buffer, and 60 min of reaction time. For human urine samples, the minimum amount of the enzyme required was 5944 units. Under these conditions, the accuracy and precision values of the 6-O-MEL determination (relative errors and standard deviation) were -3.60--0.47% and <6.80%, respectively. Finally, we analyzed the total amount of MEL metabolites excreted in 24-h urine samples; it was 6.70-11.28 µg in three subjects, which is comparable with the values reported till date. Thus, we have established a new method of measuring the total 6-O-MEL in human urine samples using an LC-MS/MS coupled with the prerequisite deconjugation reaction.
Sulfation of 6-Hydroxymelatonin, N-acetylserotonin and 4-hydroxyramelteon by the human cytosolic sulfotransferases (SULTs)
Xenobiotica 2016 Jul;46(7):612-619.PMID:26577053DOI:10.3109/00498254.2015.1107656.
1. This study aimed to investigate the involvement of sulfation in the metabolism of 6-Hydroxymelatonin (6-OH-Mel), N-acetylserotonin (NAS) and 4-hydroxyramelteon (4-OH-Ram), and to identify and characterize the human cytosolic sulfotransferases (SULTs) capable of sulfating these drug compounds. 2. A systematic analysis using 13 known human SULTs revealed that SULT1A1 displayed the strongest activity in catalyzing the sulfation of 6-OH-Mel and 4-OH-Ram, whereas SULT1C4 exhibited the strongest sulfating-activity towards NAS. pH-dependence and kinetic parameters of these SULT enzymes in mediating the sulfation of respective drug compounds were determined. A metabolic labeling study showed the generation and release of [35S]sulfated 6-OH-Mel, NAS and 4-OH-Ram by HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells labeled with [35S]sulfate in the presence of these drug compounds. Cytosols of human lung, liver, kidney and small intestine were examined to verify the presence of 6-OH-Mel-, NAS- and 4-OH-Ram-sulfating activity in vivo. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6-OH-Mel-, NAS- and 4-OH-Ram-sulfating activities than those of lung and kidney. 3. Collectively, these results provided a molecular basis for the metabolism of 6-OH-Mel, NAS and 4-OH-Ram through sulfation.
Simultaneous determination of melatonin and 6-Hydroxymelatonin in human overnight urine by LC-MS/MS
J Chromatogr B Analyt Technol Biomed Life Sci 2021 Sep 1;1181:122938.PMID:34521018DOI:10.1016/j.jchromb.2021.122938.
For the quantification of the pineal hormone melatonin and its metabolite, 6-Hydroxymelatonin, in human overnight urine, a single accurate method by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed. Urine samples were deconjugated using β-glucuronidase/arylsulfatase from Helix pomatia before solid phase extraction (SPE) purification. Chromatographic separation was performed using a reverse phase C18 column with a 7-minute gradient elution. Water was used as matrix to prepare the calibration standards, and deuterated analogues of melatonin and 6-Hydroxymelatonin were used as internal standards. This newly developed method was validated in terms of linearity, accuracy, repeatability, intermediate precision, recovery, matrix effect, and stability according to the guidelines of the European Medicines Agency. The method was successfully applied to the analysis of overnight urine samples from 12 healthy volunteers, showing significant correlations of urinary melatonin and 6-Hydroxymelatonin excretion rates with age. The urinary 6-Hydroxymelatonin to melatonin ratio was also established and will be assessed in further studies as a potential endogenous metric of CYP1A2 activity.
6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain homogenates
J Chem Neuroanat 2003 Oct;26(2):103-7.PMID:14599659DOI:10.1016/s0891-0618(03)00034-6.
Both 6-Hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynurenamine are photodegradants and enzymatic metabolites of melatonin and are known to retain equipotent activity against potassium cyanide-induced superoxide generation compared to melatonin. It is not clear whether one or both of these metabolites is responsible for this effect. The present study therefore investigates the possible manner in which 6-Hydroxymelatonin protects against oxidative stress induced by cyanide in rat brain homogenates. We examined the ability of 6-Hydroxymelatonin to scavenge KCN-induced superoxide anion generation as well as lipid peroxidation. In addition, we also examined the effect of this indole on lactate dehydrogenase activity (LDH) as well as mitochondrial electron transport using dichlorophenol-indophenol as an electron acceptor. The results of this study show that 6-Hydroxymelatonin significantly reduces KCN-induced superoxide anion generation, which is accompanied by a commensurate reduction in lipid peroxidation. Partial reversal of the KCN-induced reduction in mitochondrial electron transport is accompanied by a similar reversal of mitochondrial LDH activity blunted by KCN. It can thus be proposed that 6-Hydroxymelatonin is potentially neuroprotective against KCN-induced neurotoxicity.
6-Hydroxymelatonin protects against quinolinic-acid-induced oxidative neurotoxicity in the rat hippocampus
J Pharm Pharmacol 2005 Jul;57(7):877-81.PMID:15969947DOI:10.1211/0022357056424.
Melatonin, a naturally occurring chemical mediator, although assigned a diverse range of functions, has attracted interest because of its ability to function as a free radical scavenger. Its major hepatic metabolite and photoproduct, 6-Hydroxymelatonin (6-OHM), also shares this property. Since singlet oxygen and quinolinic acid (QUIN) are critically involved in the pathology of neurotoxicity, the objective of this study was to investigate the ability of 6-OHM to scavenge singlet oxygen and evaluate its ability to scavenge superoxide anions and reduce QUIN-induced neurotoxicity in the hippocampus in-vivo. The results show that 6-OHM is an efficient inhibitor of singlet oxygen formation as indicated by the rate constants and quantum yields reported for 6-OHM and zinc phthalocyanine (ZnPc), respectively. 6-OHM, appears to reduce QUIN-induced superoxide anion generation in the hippocampus, which provides some evidence of the neuroprotective effects of 6-OHM.