MGAT2-IN-2
目录号 : GC31555
MGAT2-IN-2是一种有效的选择性酰基辅酶A:单酰甘油酰基转移酶2(MGAT2)抑制剂，IC50为3.4nM。
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<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].
[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 | ||
| 分子式 | C26H21F5N4O4S | 分子量 | 580.53 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7226 mL | 8.6128 mL | 17.2256 mL |
| 5 mM | 0.3445 mL | 1.7226 mL | 3.4451 mL |
| 10 mM | 0.1723 mL | 0.8613 mL | 1.7226 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet