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ChemicalBook--->CAS DataBase List--->1710630-11-7

1710630-11-7

1710630-11-7 Structure

1710630-11-7 Structure
IdentificationBack Directory
[Name]

MGAT2-IN-2
[CAS]

1710630-11-7
[Synonyms]

MGAT2-IN-2
MGAT-2-IN-2,MGAT2IN2,MGAT2 IN 2
1H-Indole-1-carboxamide, 5-[[(2,4-difluorophenyl)amino]sulfonyl]-2,3-dihydro-7-(2-oxo-1-pyrrolidinyl)-N-[4-(trifluoromethyl)phenyl]-
[Molecular Formula]

C26H21F5N4O4S
[MDL Number]

MFCD31619319
[MOL File]

1710630-11-7.mol
[Molecular Weight]

580.53
Chemical PropertiesBack Directory
[density ]

1.567±0.06 g/cm3(Predicted)
[storage temp. ]

Store at -20°C
[solubility ]

Soluble in DMSO
[pka]

8.81±0.20(Predicted)
Hazard InformationBack Directory
[Uses]

MGAT2-IN-2 is a potent and selective acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) inhibitor with an IC50 of 3.4 nM.
[in vivo]

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<0.025) at doses of 10 and 30 mg/kg. A similar effect of reducing the rate of fat entrance into the circulation is observed in MGAT2 gene knockout mice[1].

[IC 50]

MGAT2: 3.4 nM (IC50)
[storage]

Store at -20°C
[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. DOI:10.1021/acs.jmedchem.5b00178
[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. DOI:10.1016/j.bmc.2015.06.003
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