Fagomine
(Synonyms: 荞麦碱; D-Fagomine) 目录号 : GC36024
Fagomine 是一种温和的糖苷酶 (glycosidase) 抑制剂，Fagomine 作用于 Amyloglucosidase (A.niger)，β-Glucosidase (bovine) 和 Isomaltase (yeast)，Ki 分别为 4.8 μM，39 μM 和 70 μM。
Cas No.:53185-12-9
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
Kinase experiment: | Lysosomal enzyme activities in cell lysates are determined. Briefly, cells are scraped in ice-cold 0.1% Triton X-100 in water. After centrifugation (6000 rpm for 15 min at 4°C) to remove insoluble materials, protein concentrations are determined using Protein Assay Rapid Kit. The lysates are incubated at 37°C with the corresponding 4-methylumbelliferyl β-D-glycopyranoside solution in 0.1 M citrate buffer (pH 4). The liberated 4-methylumbelliferone is measured with a fluorescence plate reader (excitation 340 nm; emission 460 nm). For enzyme inhibition assay, cell lysates from normal skin fibroblasts are mixed with the 4-methylumbelliferyl β-D-glycopyranoside substrates in the absence or presence of increasing concentrations of Fagomine[1]. |
Cell experiment: | Human skin fibroblasts from a healthy and three Gaucher disease patients (with N188S/G183W, V230G/R296X and L444P/L444P mutations) are maintained in our laboratory with DMEM supplemented with 10% FBS as the culture medium. For enzyme activity enhancement assay, cells are cultured in the presence of different concentrations of Fagomine or DMSO alone (as a control) for 5 days and harvested by scraping. Cytotoxicity of Fagomine is monitored by measuring the lactate dehydrogenase activities in the cultured supernatants[1]. |
Animal experiment: | Rats[3] Sprague-Dawley rats (male, 22 weeks old) are randomly assigned to one of the three dietary groups: the control group, fed a standard diet (STD); a group fed HFHS (modified high-fat high-sucrose diet); and a group fed HFHS supplemented with 0.065% Fagomine (HFHS+FG). The percentage of Fagomine is adjusted so that its ratio to sucrose is 2 mg/g, as defined before from the results of post-prandial tests.The modified diets are processed. Feed consumption is monitored every day throughout the experiment and body weight is measured before and at the end of the nutritional intervention. All animal manipulations are carried out in the morning to minimize the effects of circadian rhythms. |
References: [1]. Mena-Barragán T, et al. Inhibitor versus chaperone behaviour of d-fagomine, DAB and LAB sp2-iminosugar conjugates againstglycosidases: A structure-activity relationship study in Gaucher fibroblasts. Eur J Med Chem. 2015 Aug 31. pii: S0223-5234(15)30222-1. | |
Fagomine is a mild glycosidase inhibitor. The Ki of the iminosugar Fagomine is 4.8 μM, 39 μM, and 70 μM for Amyloglucosidase (A.niger), β-Glucosidase (bovine), and Isomaltase (yeast), respectively. Glycosidase[1]
Fagomine (D-fagomine) is an iminosugar that has been shown to selectively agglutinate Enterobacteriales in vitro. Fagomine selectively agglutinates fimbriated enterobacteria (e.g., E.coli) and inhibits their adhesion to the intestinal mucosa; the reason for this is probably related to its structural similarity with lectin-binding saccharides (e.g., mannose). Fagomine is capable of altering this effect of high-fat high-sucrose diet (HFHS) on the proportion of Enterobacteriales and E.coli[2].
Fagomine (D-fagomine) is a natural iminosugar that counteracts the short-term effects of a high-energy-dense diet on body weight, fasting blood glucose levels and the proportion of gut Enterobacteriales[3]. Compare to the standard group, rats fed high-fat high-sucrose diet (HFHS) with Fagomine (D-fagomine) gain significantly less weight (15.3%) than those fed HFHS (20.9%)[2].
[1]. Mena-BarragÁn T, et al. Inhibitor versus chaperone behaviour of d-fagomine, DAB and LAB sp2-iminosugar conjugates againstglycosidases: A structure-activity relationship study in Gaucher fibroblasts. Eur J Med Chem. 2015 Aug 31. pii: S0223-5234(15)30222-1. [2]. Ramos-Romero S, et al. Effect of (D)-fagomine on excreted Enterobacteria and weight gain in rats fed a high-fat high-sucrose diet. Obesity (Silver Spring). 2014 Apr;22(4):976-9. [3]. Molinar-Toribio E, et al. D-Fagomine attenuates metabolic alterations induced by a high-energy-dense diet in rats. Food Funct. 2015 Aug;6(8):2614-9.
| Cas No. | 53185-12-9 | SDF | |
| 别名 | 荞麦碱; D-Fagomine | ||
| Canonical SMILES | O[C@@H]1CCN[C@@H]([C@H]1O)CO | ||
| 分子式 | C6H13NO3 | 分子量 | 147.17 |
| 溶解度 | Water: ≥ 36 mg/mL (244.62 mM) | 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 | 6.7949 mL | 33.9743 mL | 67.9486 mL |
| 5 mM | 1.359 mL | 6.7949 mL | 13.5897 mL |
| 10 mM | 0.6795 mL | 3.3974 mL | 6.7949 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。
Fagomine isomers and glycosides from Xanthocercis zambesiaca
J Nat Prod 1997 Mar;60(3):312-4.PMID:9157194DOI:10.1021/np960646y.
50% aqueous MeOH extracts from the leaves and roots of Xanthocercis zambesiaca (Leguminosae) were subjected to various ion-exchange column chromatographic steps to give Fagomine (1), 3-epi-fagomine (2), 3,4-di-epi-fagomine (3), 3-O-beta-D-glucopyranosylfagomine (4), and 4-O-beta-D-glucopyranosylfagomine (5). Their structures were determined by spectroscopic analyses, particularly by extensive 1D and 2D NMR studies. Compounds 3 and 4 are new natural products. Compound 1 is a good inhibitor of isomaltase and certain alpha- and beta-galactosidases. Whereas 2 is a more potent inhibitor of isomaltase and beta-galactosidases than 1, it does not inhibit alpha-galactosidase. Compounds 3-5 exhibited no significant inhibition against the glycosidases used.
Glycal mediated synthesis of piperidine alkaloids: Fagomine, 4- epi-fagomine, 2-deoxynojirimycin, and an advanced intermediate, iminoglycal
RSC Adv 2022 Nov 17;12(51):33021-33031.PMID:36425185DOI:10.1039/d2ra05224e.
Glucal and galactal are transformed into 2-deoxyglycolactams, which are important building blocks in the synthesis of biologically active piperidine alkaloids, Fagomine and 4-epi-fagomine. In one of the strategies, reduction of 2-deoxyglycolactam-N-Boc carbonyl by lithium triethylborohydride (Super-Hydride®) has been exploited to generate lactamol whereas reduction followed by dehydration was utilized as the other strategy to functionalize the C1-C2 bond in the iminosugar substrate. The strategies provide the formal synthesis of 2-deoxynojirimycin, nojirimycin and nojirimycin B. DFT studies were carried out to determine the reason for the failure of the formation of the 2-deoxygalactonojirimycin derivative. Further, DFT studies suggest that phenyl moieties of protecting groups and lone pairs of oxygen in carbamate group plays a vital role in deciphering the conformational space of the reaction intermediates and transition-state structures through cation-π or cation-lone pair interactions. The influence of these interactions is more pronounced at low temperature when the entropy factor is small.
Correction: Glycal mediated synthesis of piperidine alkaloids: Fagomine, 4- epi-fagomine, 2-deoxynojirimycin, and an advanced intermediate, iminoglycal
RSC Adv 2022 Dec 1;12(53):34570.PMID:36545593DOI:10.1039/d2ra90122f.
[This corrects the article DOI: 10.1039/D2RA05224E.].
Potentiation of glucose-induced insulin secretion by Fagomine, a pseudo-sugar isolated from mulberry leaves
Horm Metab Res 1998 Nov;30(11):679-83.PMID:9918385DOI:10.1055/s-2007-978957.
The mechanisms of potentiation by Fagomine, an N-containing pseudo-sugar derived from mulberry leaves, of insulin secretion from isolated rat pancreatic islets in response to glucose was studied. Fagomine at more than 1 mmol/L significantly potentiated insulin secretion induced by 10 mmol/L glucose. The pseudo-sugar, however, did not affect the basal insulin secretion assessed at a glucose concentration of 3.5 mmol/L. The effects of Fagomine on 10 mmol/L and 20 mmol/L glucose-induced insulin secretion were not significantly different. Fagomine (4 mmol/L) also potentiated glyceraldehyde-induced insulin secretion, but not the leucine-induced type. Glycolysis assessed by lactate production from glucose was significantly enhanced. The amounts of all intermediates (from glucose 6-phosphate to glyceraldehyde 3-phosphate) of the upper part of the glycolytic pathway in islets incubated with 20 mmol/L glucose were not affected by 4 mmol/L Fagomine. The rise in the ATP/ADP ratio through both the glycolytic pathway and the citric acid cycle is believed to be pivotal in glucose- and glyceraldehyde-induced insulin secretion; whereas the ATP/ADP ratio rise through the citric acid cycle via the formation of acetyl-CoA is involved in leucine-induced insulin secretion. Our findings, together with these considerations, suggest that Fagomine potentiates glucose-induced insulin secretion through acceleration of some step(s) after the formation of glyceraldehyde 3-phosphate in the glycolytic pathway.
A concise synthesis of N-substituted Fagomine derivatives and the systematic exploration of their α-glycosidase inhibition
Eur J Med Chem 2014 Apr 22;77:211-22.PMID:24642564DOI:10.1016/j.ejmech.2014.03.004.
A novel and concise scheme has been developed successfully for the syntheses of N-substituted Fagomine derivatives. The transformation of lactone (2) to 1,5-diol (3) was carried on with high yield (93-95%). The cyclization of 4 to 5 is a high stereoselective reaction (de value > 98%). It is disclosed that bulky substituent at N atom of the piperidine decreases the inhibition activity except those substituents having the ability of solvation or forming disulfide bond with M444 at the active site of α-glycosidase, which enhance the interaction with enzyme. Compounds with S-configuration at C-3 show greater activity than those with R-configuration. The structure-activity relationship study is also supported by molecular docking analysis.