Benfluorex hydrochloride
(Synonyms: 盐酸苯氟雷司,JP-992 hydrochloride) 目录号 : GC35489
Benfluorex hydrochloride (JP-992 hydrochloride) 是一个肝核因子 4α (HNF4α) 激活剂。
Cas No.:23642-66-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Kinase experiment: |
HepG2 cells are treated with DMSO or Benfluorex hydrochloride at a concentration of 20 µM or 40 µM for 16 hr.Total cell protein is extracted, measured by BCA protein assay. Each sample is split into two aliquots for proteolysis without (-) or with (+) Subtilisin. Twenty ug of cell lysate is incubated with or without protease (20 ng/mL subtilisin) for 35 minutes at room temperature. Western blot is then performed with primary anti-HNF4α polyclonal antibody (1:1000 dilution) and secondary HRP conjugated anti-goat IgG (1:2000 dilution), detected with chemiluminescence ECL kit[1]. |
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Cell experiment: |
Hepatocytes are isolated by in situ perfusion of the liver with 0.025% collagenase. Hepatocytes (1 to 2×106 cells/mL) are incubated at 37°C in 2 mL of oxygenated (O2:CO2; 95:5) Krebs-Henseleit bicarbonate buffer (pH 7.4) for 1 h in a gyratory shaking water bath. Benfluorex hydrochloride is dissolved in DMSO and added (10 μL) to the incubation medium at a final concentration of 0.1 or 1 nM[2]. |
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References: [1]. Lee SH, et al. Identification of alverine and benfluorex as HNF4α activators. ACS Chem Biol. 2013 Aug 16;8(8):1730-6. |
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Benfluorex hydrochloride (JP-992 hydrochloride) is a hepatic nuclear factor 4 alpha (HNF4α) activator. HNF4α[1]
Benfluorex hydrochloride consistently activates insulin promoter activity as measured by an increased number of GFP-positive cells. Benfluorex hydrochloride increases the number of GFP-positive cells in a dose-responsive manner and increases the level of endogenous insulin mRNA. Consistent with being HNF4α activator, Benfluorex hydrochloride stimulates HNF4α expression. Benfluorex hydrochloride alters HNF4α protease sensitivity, while the inactive control compound does not[1]. Benfluorex hydrochloride decreases, in a concentration-dependent manner, the synthesis of acid-soluble products and ketone bodies from oleate, whereas the production of 14CO2 into citric acid cycle is markedly increased by Benfluorex hydrochloride. Benfluorex hydrochloride inhibits in a dose-dependent manner the rates of gluconeogenesis from lactate/pyruvate (10/1 nM)[2].
[1]. Lee SH, et al. Identification of alverine and benfluorex as HNF4α activators. ACS Chem Biol. 2013 Aug 16;8(8):1730-6. [2]. Kohl C, et al. Effects of benfluorex on fatty acid and glucose metabolism in isolated rat hepatocytes: from metabolic fluxes to gene expression. Diabetes. 2002 Aug;51(8):2363-8.
| Cas No. | 23642-66-2 | SDF | |
| 别名 | 盐酸苯氟雷司,JP-992 hydrochloride | ||
| Canonical SMILES | FC(C1=CC(CC(NCCOC(C2=CC=CC=C2)=O)C)=CC=C1)(F)F.[H]Cl | ||
| 分子式 | C19H21ClF3NO2 | 分子量 | 387.82 |
| 溶解度 | DMSO: ≥ 100 mg/mL (257.85 mM); Water: 3.33 mg/mL (8.59 mM) | 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 | 2.5785 mL | 12.8926 mL | 25.7852 mL |
| 5 mM | 0.5157 mL | 2.5785 mL | 5.157 mL |
| 10 mM | 0.2579 mL | 1.2893 mL | 2.5785 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。
Benfluorex decreases insulin resistance and improves lipid profiles in obese type 2 diabetic patients
Diabetes Metab Rev 1993 Nov;9 Suppl 1:29S-34S.PMID:8299486DOI:10.1002/dmr.5610090506.
Benfluorex hydrochloride has known lipid- and glucose-lowering effects. We evaluated the change in lipids, fasting glucose, and insulin sensitivity in ten obese type 2 diabetic patients after treatment with benfluorex or a placebo for 2 weeks using a double-blind, cross-over design. Insulin sensitivity was measured using the euglycaemic-hyperinsulinaemic glucose clamp technique at two insulin infusion rates for 2 h each: 0.05 U/kg per h (clamp 1) and 0.10 U/kg per h (clamp 2). Mean fasting glucose decreased from 13.1 +/- 1.1 to 10.2 +/- 0.9 mmol/l after benfluorex (p < 0.001) and rose from 11.9 +/- 0.9 to 13.3 +/- 1.0 mmol/l after the placebo (p = 0.028). Insulin did not change significantly. Glucose uptake (GU) as a parameter for insulin sensitivity was compared for treatment with benfluorex versus the placebo. Total GU during clamp 1 was 643.4 +/- 323.8 mmol after benfluorex and 250.1 +/- 193.3 mmol after the placebo (p = 0.035), and during clamp 2, 2490.7 +/- 490.5 mmol after benfluorex and 1544.3 +/- 693.9 mmol after the placebo (p = 0.018). The dynamic analysis on the last 30 min of clamp 2 showed a significant difference in glucose infusion rate (GIR) profile, with mean levels yielding 5.36 mmol/kg per min after benfluorex and 3.87 mmol/kg per min after the placebo (p = 0.018); there were no differences in plasma insulin concentrations or plasma glucose levels. It is concluded that in this short-term study benfluorex increases insulin sensitivity in obese type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Thermal and X-ray powder diffraction structural characterization of two Benfluorex hydrochloride polymorphs
J Pharm Biomed Anal 2010 Sep 21;53(1):1-6.PMID:20347245DOI:10.1016/j.jpba.2010.02.037.
Two polymorphic forms of Benfluorex hydrochloride, phases I and II, were isolated as monophasic polycrystalline samples, and structurally characterized using ab initio X-ray powder diffraction methods and a global optimization strategy (simulated annealing). Form I crystallizes in monoclinic system, space group P2(1)/n, with Z=4, a=21.0719(10)A, b=7.0563(4)A, c=14.8684(7)A, beta=116.998(3) degrees , V=1969.8(2)A(3), while Form II crystallizes in the orthorhombic space group Pbca, with Z=8, a=33.8031(2)A, b=15.1451(8)A, c=7.6138(6)A, V=3897.9(4)A(3). Crystals of Form I and Form II of Benfluorex hydrochloride are based upon an ionic packing of protonated benfluorex molecules at the most basic site, the N1 atoms, and chloride anions. Form I shows the presence of mu-Cl ions, generating centrosymmetric dimers with a N(2)Cl(2) moiety, while Form II contains antiparallel chains of C-H...O hydrogen-bonded molecules running along c axis. DSC and thermodiffractometric measurements showed that heating progressively Form II from ambient temperature to 160 degrees C causes a phase transition to the thermodynamically stable Form I, immediately followed by the sample melting, near 165 degrees C. Recrystallization directly to Form I is observed when the melt is cooled back to ambient temperature, with a significant hysteresis (this event being centered near 130 degrees C).