AFMK
(Synonyms: N-Γ-乙酰基-N-2-甲酰-5-甲氧基犬尿氨酸) 目录号 : GC41371An antioxidant metabolite of melatonin
Cas No.:52450-38-1
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
Melatonin is a neurotransmitter widely distributed in eukaryotes and is closely linked to circadean rhythms in mammals including humans. AFMK is a melatonin metabolite first identified in rat brain. AFMK has antioxidant and free radical scavenging activities in several experimental models. AFMK may also be measured in plasma as an index of melatonin synthesis and metabolism.
| Cas No. | 52450-38-1 | SDF | |
| 别名 | N-Γ-乙酰基-N-2-甲酰-5-甲氧基犬尿氨酸 | ||
| Canonical SMILES | O=CNc1ccc(OC)cc1C(=O)CCNC(=O)C | ||
| 分子式 | C13H16N2O4 | 分子量 | 264.3 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 5 mg/ml,PBS (pH 7.2): 1 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 | 3.7836 mL | 18.9179 mL | 37.8358 mL |
| 5 mM | 0.7567 mL | 3.7836 mL | 7.5672 mL |
| 10 mM | 0.3784 mL | 1.8918 mL | 3.7836 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。
On the free radical scavenging activities of melatonin's metabolites, AFMK and AMK
J Pineal Res 2013 Apr;54(3):245-57.PMID:22998574DOI:10.1111/jpi.12010.
The reactions of N(1) -acetyl-N(2) -formyl-5-methoxykynuramine (AFMK) and N(1) -acetyl-5-methoxykynuramine (AMK) with (•) OH, (•) OOH, and •OOCCl3 radicals have been studied using the density functional theory. Three mechanisms of reaction have been considered: radical adduct formation (RAF), hydrogen transfer (HT), and single electron transfer (SET). Their relative importance for the free radical scavenging activity of AFMK and AMK has been assessed. It was found that AFMK and AMK react with •OH at diffusion-limited rates, regardless of the polarity of the environment, which supports their excellent •OH radical scavenging activity. Both compounds were found to be also very efficient for scavenging •OOCCl3 , but rather ineffective for scavenging •OOH. Regarding their relative activity, it was found that AFMK systematically is a poorer scavenger than AMK and melatonin. In aqueous solution, AMK was found to react faster than melatonin with all the studied free radicals, while in nonpolar environments, the relative efficiency of AMK and melatonin as free radical scavengers depends on the radical with which they are reacting. Under such conditions, melatonin is predicted to be a better •OOH and •OOCCl3 scavenger than AMK, while AMK is predicted to be slightly better than melatonin for scavenging •OH. Accordingly it seems that melatonin and its metabolite AMK constitute an efficient team of scavengers able of deactivating a wide variety of reactive oxygen species, under different conditions. Thus, the presented results support the continuous protection exerted by melatonin, through the free radical scavenging cascade.
Evaluation of melatonin and AFMK levels in women with breast cancer
Endocrine 2018 Oct;62(1):242-249.PMID:29797213DOI:10.1007/s12020-018-1624-2.
Purpose: Changes in the circadian rhythm may contribute to the development of cancer and are correlated with the high risk of breast cancer (BC) in night workers. Melatonin is a hormone synthesized by the pineal gland at night in the absence of light. Levels of melatonin and the metabolite of oxidative metabolism AFMK (acetyl-N-formyl-5-methoxykynurenamine), are suggested as potential biomarkers of BC risk. The aims of this study were to evaluate levels of melatonin and AFMK in women recently diagnosed with BC, women under adjuvant chemotherapy, and night-shift nurses, and compare them with healthy women to evaluate the relation of these compounds with BC risk. Methods: Blood samples were collected from 47 women with BC, 9 healthy women, 10 healthy night shift nurses, and 6 patients under adjuvant chemotherapy. Compound levels were measured by mass spectrometry. Results and conclusions: Our results showed that women with BC had lower levels of melatonin compared to control group women, and even lower in night-shift nurses and in patients under adjuvant chemotherapy. There was no significant difference of AFMK levels between the groups. In addition to this, high levels of melatonin and AFMK were related to patients with metastasis, and high levels of AFMK were related to the presence of lymph node-positive, tumor > 20 mm and patients who sleep with light at night. Our results showed a reduction of melatonin levels in BC patients, suggesting a relation with the disease, and in addition, point to the importance of melatonin supplementation in women that work at night to reduce the BC risk.
AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice
J Pineal Res 2007 Apr;42(4):386-93.PMID:17439555DOI:10.1111/j.1600-079X.2007.00432.x.
Antioxidant function of melatonin is well established. However, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a melatonin metabolite is a sparingly investigated biogenic amine, especially in relation to its in vivo antioxidant function. We have evaluated the oxidative damage to biomolecules (DNA, protein and lipid) induced by X-irradiation in C57BL mice and the prophylactic action of AFMK. The extent of DNA damage was analyzed by single-cell gel electrophoresis in cerebral cortex and serum 8-hydroxydeoxyguanosine (8-OHdG) levels by enzyme-linked immunosorbent assay. Oxidative modification of protein and lipid was measured in the terms of carbonyl content and 4-HAE + MDA (4-hydroxyalkenal + malondialdehyde) status of brain cortex. Radiation exposure dramatically augmented the level of 8-OHdG in serum as well as DNA migration in the comet tail. AFMK pretreatment significantly inhibited DNA damage. In addition, radiation-induced augmentation of protein carbonyl content and HAE + MDA was ameliorated by AFMK pretreatment. Whole-body exposure of mice to X-irradiation also reduced the level of brain sulfhydryl contents (protein-bound sulfhydryl, total sulfhydryl, and nonprotein sulfhydryl) which were significantly protected by AFMK. Radiation-induced decline in the total antioxidant capacity of plasma was significantly reversed in AFMK pretreated mice. Moreover, AFMK showed a very high level of in vitro hydroxyl radical scavenging potential which was measured by an electron spin resonance (ESR) study of the 2-hydroxy-5,5-dimethyl-1-pyrrolineN-oxide (DMPO-OH) adduct. IC(50) values resulting from ESR analysis was 338.08 nm. The present study indicate that AFMK is a potent antioxidant in both in vivo and in vitro systems.
Melatonin metabolism, signaling and possible roles in plants
Plant J 2021 Jan;105(2):376-391.PMID:32645752DOI:10.1111/tpj.14915.
Melatonin is a multifunctional biomolecule found in both animals and plants. In this review, the biosynthesis, levels, signaling, and possible roles of melatonin and its metabolites in plants is summarized. Tryptamine 5-hydroxylase (T5H), which catalyzes the conversion of tryptamine into serotonin, has been proposed as a target to create a melatonin knockout mutant presenting a lesion-mimic phenotype in rice. With a reduced anabolic capacity for melatonin biosynthesis and an increased catabolic capacity for melatonin metabolism, all plants generally maintain low melatonin levels. Some plants, including Arabidopsis and Nicotiana tabacum (tobacco), do not possess tryptophan decarboxylase (TDC), the first committed step enzyme required for melatonin biosynthesis. Major melatonin metabolites include cyclic 3-hydroxymelatonin (3-OHM) and 2-hydroxymelatonin (2-OHM). Other melatonin metabolites such as N1 -acetyl-N2 -formyl-5-methoxykynuramine (AFMK), N-acetyl-5-methoxykynuramine (AMK) and 5-methoxytryptamine (5-MT) are also produced when melatonin is applied to Oryza sativa (rice). The signaling pathways of melatonin and its metabolites act via the mitogen-activated protein kinase (MAPK) cascade, possibly with Cand2 acting as a melatonin receptor, although the integrity of Cand2 remains controversial. Melatonin mediates many important functions in growth stimulation and stress tolerance through its potent antioxidant activity and function in activating the MAPK cascade. The concentration distribution of melatonin metabolites appears to be species specific because corresponding enzymes such as M2H, M3H, catalases, indoleamine 2,3-dioxygenase (IDO) and N-acetylserotonin deacetylase (ASDAC) are differentially expressed among plant species and even among different tissues within species. Differential levels of melatonin and its metabolites can lead to differential physiological effects among plants when melatonin is either applied exogenously or overproduced through ectopic overexpression.
Melatonin and its metabolite N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) enhance chemosensitivity to gemcitabine in pancreatic carcinoma cells (PANC-1)
Pharmacol Rep 2018 Dec;70(6):1079-1088.PMID:30308458DOI:10.1016/j.pharep.2018.05.007.
Background: Gemcitabine is a standard chemotherapeutic agent for patients suffering from pancreatic cancer. However, the applied therapy is not effective due to the resistance of tumor cells to cytostatics, caused by inefficiency of the apoptotic mechanisms. Herein, we present the hypothesis that melatonin and its metabolite N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) modify the effect of gemcitabine on PANC-1 cells and that this phenomenon is dependent on the modulation of apoptosis. Methods: PANC-1 cells have been incubated with melatonin, AFMK or gemcitabine alone or in combination to determine the cytotoxity and proliferative effects. In subsequent part of the study, cells were harvested, the proteins were isolated and analyzed employing immunoprecipitation/immunoblotting. Results: Incubation of PANC-1 cells with gemcitabine resulted in upregulation of pro-apoptotic bax and caspases proteins expression, downregulation of anti-apoptotic Bcl-2, heat shock proteins (HSPs) and modulation of cellular inhibitors of apoptosis (IAPs). Both melatonin and AFMK administered to PANC-1 in combination with gemcitabine inhibited the production of HSP70 and cIAP-2 as compared to the results obtained with gemcitabine alone. These changes were accompanied by upregulation of Bax/Bcl-2 ratio and reduction of procaspases-9 and -3 abundance, followed by an increase in the formation of active caspase of PANC-1 cells with combination of gemcitabine plus low doses of melatonin or AFMK led to enhanced cytotoxicity and resulted in the inhibition of PANC-1 cells growth as compared to effects of gemcitabine alone. Conclusion: Melatonin and AFMK could improve the anti-tumor effect of gemcitabine in PANC-1 cells presumably through the modulation of apoptotic pathway.