MGAT2-IN-2 |
Catalog No.GC31555
One-Click Copy Product Info
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MGAT2-IN-2 es un inhibidor potente y selectivo de acil CoA:monoacilglicerol aciltransferasa 2 (MGAT2) con una IC50 de 3,4 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1710630-11-7
Sample solution is provided at 25 µL, 10mM.
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MGAT2-IN-2 is a potent and selective acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) inhibitor with an IC50 of 3.4 nM.
MGAT2-IN-2 (Compound 24d) exhibits potent MGAT2 inhibitory activity with an IC50 value of 3.4 nM and a ligand lipophilicity efficiency (LLE) value of 5.4[1]. MGAT2-IN-2 (Compound 2) exhibits time-dependent inhibition (TDI) of cytochrome P450 3A4 (CYP3A4). Preincubation of MGAT2-IN-2 with microsomes leads to a significant loss of the activity of CYP3A4 relative to that under a condition without preincubation[2].
Effect of MGAT2-IN-2 on plasma TG is elevated during the oral fat tolerance test in C57BL/6J mice. MGAT2-IN-2 (3, 10 and 30 mg/kg) is orally administered 6 h prior to oil challenge. Pharmacokinetic studies reveal that MGAT2-IN-2 displays a high plasma concentration (AUC0-8h=842 ng•h/mL) and favorable oral bioavailability (F=52%), which are probably driven by the improved stability against oxidative metabolism and hydrolysis. For evaluating the in vivo efficacy, MGAT2-IN-2 is examined for its effect on hypertriglyceridemia during oral fat tolerance test (OFTT) using C57BL/6J mice. To inhibit the hydrolysis of plasma triacylglycerol (TG) by lipoprotein lipase (LPL), mice are pretreated with an LPL inhibitor, Pluronic F127, permitting measurement of the accumulation of plasma TG following olive oil administration. MGAT2-IN-2 and vehicle are administered 6 h before the oral olive oil load, and plasma chylomicron TG concentrations are monitored for 4 h. MGAT2-IN-2 effectively and dose-dependently suppresses plasma TG elevation after olive oil challenge. The TG-lowering effect of MGAT2-IN-2 is significant (p
[1]. Sato K, et al. Discovery of a Novel Series of N-Phenylindoline-5-sulfonamide Derivatives as Potent, Selective, and Orally Bioavailable Acyl CoA:Monoacylglycerol Acyltransferase-2 Inhibitors. J Med Chem. 2015 May 14;58(9):3892-909. [2]. Sato K, et al. Optimization of a novel series of N-phenylindoline-5-sulfonamide-based acylCoA:monoacylglycerol acyltransferase-2 inhibitors: Mitigation of CYP3A4 time-dependent inhibition and phototoxic liabilities. Bioorg Med Chem. 2015 Aug 1;23(15):4544-60.
Kinase experiment: | The test compounds (e.g., MGAT2-IN-2) are dissolved in 5 μL of an assay buffer, which consists of 100 mM Tris-HCl (pH 7.5), 5 mM MgCl2, 200 mM sucrose, 0.01% Tween 20, 2 mM DTT, 0.01% BSA and 5% DMSO and incubated with 10 μL of 0.6 μg/mL MGAT2 enzyme for 60 min. The reaction is started with the addition of 5 μL of 13C×18 oleoyl-CoA and 2-oleoyl-glycerol at 20 μM each. After incubation at rt for 30 min, the reaction is stopped with Acetonitrile containing 0.88% formic acid and 1.3 μM 1,2-dioleoyl-glycerol as an internal standard. High-throughput online solid phase extraction is performed using a RapidFire 300. Mass spectrometric analysis is performed using an API-4000 triple quadrupole mass spectrometer in positive SRM mode[1]. |
Animal experiment: | Mice[1]Male C57BL/6J mice (20-25 g) are used in the OFTT study. The animals are fed with standard chow and tap water ad libitum, maintained at 23±3 °C with a constant humidity of 40-70%, and acclimated with a cycle of 12 h of light and 12 h of darkness. Overnight fasted mice are orally treated with a single dose of 3, 10 and 30 mg/kg body weight of MGAT2-IN-2. At 6 h after the treatment of MGAT2-IN-2, mice are orally given 8 mL/kg olive oil or water. |
References: [1]. Sato K, et al. Discovery of a Novel Series of N-Phenylindoline-5-sulfonamide Derivatives as Potent, Selective, and Orally Bioavailable Acyl CoA:Monoacylglycerol Acyltransferase-2 Inhibitors. J Med Chem. 2015 May 14;58(9):3892-909. | |
| Cas No. | 1710630-11-7 | SDF | |
| Canonical SMILES | O=C(N1CCC2=C1C(N3C(CCC3)=O)=CC(S(=O)(NC4=CC=C(F)C=C4F)=O)=C2)NC5=CC=C(C(F)(F)F)C=C5 | ||
| Formula | C26H21F5N4O4S | M.Wt | 580.53 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7226 mL | 8.6128 mL | 17.2256 mL |
| 5 mM | 344.5 μL | 1.7226 mL | 3.4451 mL |
| 10 mM | 172.3 μL | 861.3 μL | 1.7226 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)