| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: = 98.67%
| Targets |
Natural Triterpenes/limonoid; anti-obesity; anti-hyperglycemic
Nomilin targets multiple pathways, including the MAPK pathway. It is an inducer of Phase II detoxifying enzymes (e.g., glutathione S-transferase) and an inhibitor of chemically induced carcinogenesis. It also inhibits HIV-1 protease. |
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| ln Vitro |
In multiple species, ML375 has been found to exhibit low predicted hepatic clearance (CLhep; human, 2.3 mL/min/kg, cynomolgus monkey, 14 mL/min/kg, rat, 18 mL/min/kg) and high metabolic stability. Additionally, ML375 has been found to have low hepatic microsomal intrinsic clearance (CLint; human 2.6 mL/min/kg, cyno 20 mL/min/kg, rat 24 mL/min/kg) [1].When lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) were reduced in hypoxic glucose deprivation (OGD)-induced cell death in SH-SY5Y cells, nomilin treatment nearly completely prevented this phenomenon [1].
In vitro, Nomilin significantly retards endothelial cell proliferation, invasion, migration, and tube formation. It mitigates cell death and decreases lactate dehydrogenase (LDH) release and ROS production in SH-SY5Y cells. It has antioxidant activity 2.9-8.3 times that of Vitamin C. |
| ln Vivo |
In MCAO rats, nomilin can reduce disruption of the blood-brain barrier (BBB), which may be related to reducing the loss of tight junction proteins such occludin-5 and ZO-1 [1].
Oxidative stress is considered to play an important role in the cerebral ischemia-reperfusion injury. The nuclear transcription factor erythroid-2-related factor 2 (Nrf2)/NAD(P)H dehydrogenase [quinone] 1 (NQO1) pathway has been considered as a potential target for neuroprotection in cerebral ischemia-reperfusion injury. Nomilin (NOM) is a limonoid compound obtained from the extracts of citrus fruits. The purpose of our study was to determine whether NOM could exert beneficial effects in cerebral ischemia-reperfusion rats. NOM improved infarct area, brain edema and neurological deficits in an experimental stroke rat model via middle cerebral artery occlusion (MCAO). Furthermore, NOM attenuated blood-brain barrier (BBB) disruption in MCAO rats, which might be associated with alleviating the loss of tight junction proteins, including ZO-1 and occludin-5. Further results revealed that NOM treatment effectively mitigated oxidative stress and facilitated the expressions of Nrf2 and NQO1, which might confirm that the loss of tight junction proteins in the microvasculature was likely mediated by oxidative stress. In conclusion, our study provided evidence that the protective effects of NOM in cerebral ischemia-reperfusion rats were related to the Nrf2/NQO1 pathway. In vivo, Nomilin induces Phase II enzymes by increasing the expression of glutathione-S-transferase and NADPH:Quinone reductase. It inhibits carcinogenesis in the hamster buccal pouch assay. It also shortens anaesthetic-induced sleeping time in mice, suggesting a stimulant action on the central nervous system. |
| Enzyme Assay |
In vitro enzyme assays for Nomilin typically involve measuring its ability to induce Phase II detoxifying enzyme activity. For example, glutathione S-transferase (GST) activity can be measured in cell lysates using a spectrophotometric assay with a substrate like 1-chloro-2,4-dinitrobenzene (CDNB). NAD(P)H:quinone reductase (QR) activity is measured using menadione or other quinone substrates.
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| Cell Assay |
NOM treatment significantly mitigated cell death and decreased lactate dehydrogenase (LDH) release and ROS production in SH-SY5Y cells induced by oxygen–glucose deprivation (OGD), which was almost abolished by Nrf2 knockdown [1].
In vitro cellular assays for Nomilin are conducted on various cancer cell lines (e.g., SH-SY5Y neuroblastoma, endothelial cells, breast cancer cells) to assess its anti-proliferative, anti-angiogenic, and cytoprotective effects. Cells are treated with the compound, and endpoints include cell viability (MTT), apoptosis (caspase-3/annexin V), migration (scratch assay), and tube formation (Matrigel assay). ROS production is measured using fluorescent probes. |
| Animal Protocol |
NOM improved infarct area, brain edema and neurological deficits in an experimental stroke rat model via middle cerebral artery occlusion (MCAO). Furthermore, NOM attenuated blood–brain barrier (BBB) disruption in MCAO rats, which might be associated with alleviating the loss of tight junction proteins, including ZO-1 and occludin-5. Further results revealed that NOM treatment effectively mitigated oxidative stress and facilitated the expressions of Nrf2 and NQO1, which might confirm that the loss of tight junction proteins in the microvasculature was likely mediated by oxidative stress [1].
In vivo animal studies for Nomilin use mouse models to study its anti-obesity and anti-hyperglycemic effects. Mice are fed a high-fat diet and treated with the compound, and parameters such as body weight, glucose tolerance, and lipid profile are measured. Carcinogenesis models (e.g., hamster buccal pouch) are used to assess its chemopreventive activity. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Nomilin are limited. As a natural product, it is expected to be absorbed and metabolized. Studies in animal models indicate it is bioavailable and can exert systemic effects. Further detailed PK characterization is needed.
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| Toxicity/Toxicokinetics |
Nomilin is considered to have a low toxicity profile. It is a natural compound found in citrus fruits and has been consumed as part of the diet for centuries. No significant toxicity has been reported in the available literature at the doses used in studies.
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| References | |
| Additional Infomation |
Nomiline is a limonene compound.
1-(acetoxy)-1,2-dihydroobacunolone has been reported to be found in Microula sikkimensis, Citrus reticulata, and other organisms with relevant data. Recent scientific research supports the view that bile acids (cholesterol metabolites) are biologically active signaling molecules that can function as ligands for the farnesoid X receptor or the G protein-coupled receptor TGR5. Through these receptors, bile acids can maintain not only bile acid homeostasis but also lipid and carbohydrate homeostasis. An interesting finding on the role of TGR5 in energy metabolism and glucose homeostasis suggests that targeting this receptor to increase thermogenesis and incretin secretion may be a potential approach to combat obesity and insulin resistance. In this review, I summarize the latest research findings related to TGR5 agonists, particularly the citrus limonene nomiline, and the role of these agonists in energy metabolism and glucose homeostasis. [2] Nomilin is a limonoid compound isolated from citrus fruits. It is an inducer of Phase II detoxifying enzymes and has shown promising chemopreventive, anti-obesity, and anti-inflammatory activities. It is not an approved drug but is widely used in research for its various biological properties. |
| Molecular Formula |
C28H34O9
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|---|---|
| Molecular Weight |
514.5642
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| Exact Mass |
514.22
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| Elemental Analysis |
C, 65.36; H, 6.66; O, 27.98
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| CAS # |
1063-77-0
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| PubChem CID |
72320
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| Appearance |
White to off-white solid
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
657.7±55.0 °C at 760 mmHg
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| Melting Point |
278-279°
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| Flash Point |
351.6±31.5 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.575
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| Source |
citrus fruits
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| LogP |
2.47
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
37
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| Complexity |
1080
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| Defined Atom Stereocenter Count |
9
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| SMILES |
O1[C@]2([H])C(=O)O[C@]([H])(C3=C([H])OC([H])=C3[H])[C@]3(C([H])([H])[H])C([H])([H])C([H])([H])[C@]4([H])[C@@]5(C([H])([H])[H])[C@@]([H])(C([H])([H])C(=O)OC(C([H])([H])[H])(C([H])([H])[H])[C@]5([H])C([H])([H])C([C@@]4(C([H])([H])[H])[C@]132)=O)OC(C([H])([H])[H])=O
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| InChi Key |
KPDOJFFZKAUIOE-WNGDLQANSA-N
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| InChi Code |
InChI=1S/C28H34O9/c1-14(29)34-19-12-20(31)36-24(2,3)17-11-18(30)27(6)16(26(17,19)5)7-9-25(4)21(15-8-10-33-13-15)35-23(32)22-28(25,27)37-22/h8,10,13,16-17,19,21-22H,7,9,11-12H2,1-6H3/t16-,17+,19+,21+,22-,25+,26-,27+,28-/m1/s1
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| Chemical Name |
1-(Acetyloxy)-1,2-dihydroobacunoic acid e-lactone
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| Synonyms |
Nomilin; 1063-77-0; 1-(acetyloxy)-1,2-dihydroobacunoic acid e-lactone; DRM0753K4T; Nomilin (~85%); (1S,3aS,4aR,4bR,6aR,11S,11aR,11bR,13aS)-1-(Furan-3-yl)-4b,7,7,11a,13a-pentamethyl-3,5,9-trioxohexadecahydrooxepino[4',3':3,4]benzo[1,2-f]oxireno[2,3-d]isochromen-11-yl acetate; AC1L2HUM; 1-(Acetyloxy)-1,2-dihydroobacunoic acid eta-lactone;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~194.34 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9434 mL | 9.7170 mL | 19.4341 mL | |
| 5 mM | 0.3887 mL | 1.9434 mL | 3.8868 mL | |
| 10 mM | 0.1943 mL | 0.9717 mL | 1.9434 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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