| 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 |
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Purity: = 98.67%
| Targets |
Natural Triterpenes/limonoid; anti-obesity; anti-hyperglycemic
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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].
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| 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. |
| 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].
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| 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].
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| References | |
| Additional Infomation |
Nomilin is a limonoid.
1-(Acetyloxy)-1,2-dihydroobacunoic acid e-lactone has been reported in Microula sikkimensis, Citrus reticulata, and other organisms with data available. Recent scientific findings support the notion that bile acids, which are cholesterol catabolites, are bioactive signaling molecules that function as ligands for the farnesoid X receptor or a G-protein-coupled receptor, TGR5. Through these receptors, bile acids can maintain not only bile acid homeostasis but also lipid and carbohydrate homeostasis. An intriguing finding regarding the role of TGR5 in energy metabolism and glucose homeostasis suggests a potential approach to combat obesity and insulin resistance by targeting this receptor to increase thermogenesis and incretin secretion. In this review, I have summarized the latest findings related to TGR5 agonists, in particular, a citrus limonoid, nomilin, and the roles of these agonists in energy metabolism and glucose homeostasis.[2] |
| 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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