| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
NB-598 maleate is a novel, highly potent and competitive inhibitor of squalene epoxidase (SE), suppressing triglyceride biosynthesis through the farnesol pathway. NB-598 significantly inhibited both basal and glucose-stimulated insulin secretion from mouse pancreatic islets. CaV channels were markedly inhibited by NB-598.
| Targets |
SE/squalene epoxidase
|
|---|---|
| ln Vitro |
NB-598 Maleate (10 μM) decreases total cholesterol levels in MIN6 cells by 36±7%. NB-598 Maleate significantly lowered cholesterol in the PM, ER, and SG by 49±2%, 46±7%, and 48±2%, respectively. NB598 at concentrations up to 10 μM did not influence the acute outward KV of the current or the voltage dependency of the enhanced activation. , but it will be removed by current [1]. NB-598 maleic acid (10 μM) inhibits the production of sterols and sterol esters from [14C]acetic acid without influencing the synthesis of other electrolytes such as phospholipids (PL), free ions (FFA), and triglycerides (TG). In the absence of exogenous electrolyte phospholipids, NB-598 maleic acid can lower ACAT activity by 31% in the presence of 600 PM sleep in vivo, and NB-598 maleic acid staining can reduce ACAT activity by 22% [2]. NB-598 maleic acid colors HepG evenly 2 cells into sleep and sleep body triglycerides [3].
|
| ln Vivo |
NB-598, (E)N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3'-bith iophen-5-yl)methoxy]benzene-methanamine, was found to inhibit human microsomal squalene epoxidase (from Hep G2 cells) in a competitive manner. NB-598 inhibited cholesterol synthesis from [14C]acetate dose dependently in Hep G2 cells and increased the intracellular radioactivity of squalene. A single oral administration of NB-598 inhibited cholesterol synthesis from [14C]acetate in rats. Moreover, multiple oral administration of NB-598 to dogs decreased serum total and low density lipoprotein cholesterol levels and increased serum squalene levels. After termination of treatment, the reduced serum cholesterol and increased squalene levels returned to their control values[4].
|
| Enzyme Assay |
NB-598, a specific inhibitor of squalene epoxidase, suppressed the secretion of cholesterol and triacylglycerol from HepG2 cells into the medium. L-654,969, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibited the secretion of cholesterol as potently as NB-598, but did not suppress the secretion of triacylglycerol. Both compounds decreased the intracellular cholesterol content almost equally, and neither of the compounds reduced the intracellular triacylglycerol content. The suppression of lipid secretion by NB-598 was associated with a significant reduction in apolipoprotein (apo) B secretion into the medium. Therefore, the suppression of lipid secretion by NB-598 may be caused by a reduction in the number of triacylglycerol-rich lipoprotein particles. In contrast, the suppression of cholesterol secretion by L-654,969 may be due to a modulation of lipoprotein lipid composition, since this agent did not reduce the secretion of apo B or triacylglycerol. The secretion of apo A-I was unaffected by either NB-598 or L-654,969. Pulse chase studies using [35S]methionine showed that the suppression of apo B secretion by NB-598 depended on an enhancement of intracellular degradation of apo B. These results indicate that the secretion of apo B from HepG2 cells is not regulated by the lipid synthesis alone, and suggest that the mechanism of the hypolipidemic effect of NB-598 involves the suppression of triacylglycerol-rich lipoprotein secretion from the liver as well as an inhibition of cholesterol synthesis in the liver[3].
|
| Cell Assay |
Subcellular fractionation of plasma membranes, endoplasmic reticulum, and insulin secretory granules[1]
MIN6 cells (4 × 108) were cultured for 48 h at 37 C in the culture medium supplemented with 10% delipidated FBS, in the absence or presence of 10 μM NB598. The cells were harvested and homogenized in fractionation buffers: 50 mM 2-(N-morpholino) ethane sulfonic acid (MES), 250 mM sucrose (pH 7.2) for plasma membrane (PM) and endoplasmic reticulum (ER); 10 mM 3[N-morholino]propanesulfonic acid-Tris, 270 mM sucrose (pH 6.8) for insulin secretory granules (SG). Fractionations for PM and ER were performed by sucrose density gradient ultracentrifugation established by Ramanadham et al. Insulin secretory granules were fractionated with Histodenz gradient ultracentrifugation followed by Percoll purification, as established by Brunner et al. The isolated subcellular fractions were stored at −20 C for protein concentration determination and cholesterol extraction.
Cholesterol content assay[1] MIN6 cells (5 × 105) or 20 pancreatic islets from mouse or human were cultured for 48 h at 37 C in the relative culture media supplemented with 10% delipidated FBS, in the absence or presence of 10 μM cholesterol biosynthesis inhibitor NB598. Cells and islets were collected and washed with PBS. Cholesterol was extracted by adding 50 μl of 2:1 chloroform-methanol mixture, followed by 100 μl of PBS. To extract cholesterol from subcellular fractions, 50 μl of 2:1 chloroform-methanol mixture was added to different compartments. The top water phase was removed after centrifugation for 3 min at 10,000 rpm. Cholesterol sample was dried and dissolved in 10–40 μl of immunoprecipitation buffer containing (in millimoles) 150 NaCl, 20 Tris-HCl, 5 MgSO4, 1 EDTA, 1 EGTA, and 1% Triton X-100. Cholesterol content was measured using a fluorescence assay kit, following the manufacturer’s instructions. |
| References |
[1]. Xia F, et al. Inhibition of cholesterol biosynthesis impairs secretion and voltage-gated calcium channel function in pancreatic beta-cells. Endocrinology. 2008 Oct;149(10):5136-45.
[2]. Horie M, et al. Effects of NB-598, a potent squalene epoxidase inhibitor, on the apical membrane uptake of cholesterol and basolateral membrane secretion of lipids in Caco-2 cells. Biochem Pharmacol. 1993 Jul 20;46(2):297-305. [3]. Horie M, et al. An inhibitor of squalene epoxidase, NB-598, suppresses the secretion of cholesterol and triacylglycerol and simultaneously reduces apolipoprotein B in HepG2 cells. Biochim Biophys Acta. 1993 May 20;1168(1):45-51. [4]. NB-598: a potent competitive inhibitor of squalene epoxidase. J Biol Chem . 1990 Oct 25;265(30):18075-8. |
| Molecular Formula |
C₃₁H₃₅NO₅S₂
|
|---|---|
| Molecular Weight |
565.74
|
| Exact Mass |
565.196
|
| CAS # |
155294-62-5
|
| Related CAS # |
NB-598;131060-14-5;NB-598 hydrochloride;136719-25-0
|
| PubChem CID |
71576679
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
7.195
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
39
|
| Complexity |
747
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(O)/C=C\C(O)=O.CC(C)(C)C#C/C=C/CN(CC)CC1=CC(OCC2=CC(C3=CSC=C3)=CS2)=CC=C1
|
| InChi Key |
QGUWPAYJKVJWEK-JVTXGDFZSA-N
|
| InChi Code |
InChI=1S/C27H31NOS2.C4H4O4/c1-5-28(14-8-6-7-13-27(2,3)4)18-22-10-9-11-25(16-22)29-19-26-17-24(21-31-26)23-12-15-30-20-23;5-3(6)1-2-4(7)8/h6,8-12,15-17,20-21H,5,14,18-19H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b8-6+;2-1-
|
| Chemical Name |
(Z)-but-2-enedioic acid;(E)-N-ethyl-6,6-dimethyl-N-[[3-[(4-thiophen-3-ylthiophen-2-yl)methoxy]phenyl]methyl]hept-2-en-4-yn-1-amine
|
| Synonyms |
NB598; NB 598; NB-598; NB-598 (Maleate); NB-598 Maleate; 155294-62-5; 136719-26-1; (Z)-but-2-enedioic acid;(E)-N-ethyl-6,6-dimethyl-N-[[3-[(4-thiophen-3-ylthiophen-2-yl)methoxy]phenyl]methyl]hept-2-en-4-yn-1-amine; NB598 Maleate salt; NB-598xMaleicacidsalt; NB-598 xMaleic acid salt;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~176.76 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.42 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 (4.42 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7676 mL | 8.8380 mL | 17.6760 mL | |
| 5 mM | 0.3535 mL | 1.7676 mL | 3.5352 mL | |
| 10 mM | 0.1768 mL | 0.8838 mL | 1.7676 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
