γ-Oryzanol - DNA Methyltransferase 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemE-OryzanolCat. No.: HY-B2194CAS No.: 11042-64-1分式: CHO分量: 602.89作靶点: DNA Methyltransferase作通路: Epigenetics储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 62.5 mg/mL (103.67 mM; Need ultrason

2、ic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (3.45 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (3.45 mM); Suspended solution; Need ultrasonic and warming3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedC

3、hemESolubility: 2.08 mg/mL (3.45 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 -Oryzanol 有效抑制纹状体中的 DNA 甲基转移酶 (DNMTs)。 抑制 DNMT1 和 DNMT3a，IC50 分别为3.2 M 和 22.3 M。IC50 & Target DNMT1 DNMT3A3.2 M (IC50) 22.3 M (IC50)体外研究 -Oryzanol significantly inhibits the activities of DNMT1 (IC50=3.2 M), DNMT 3a (IC50=22.

4、3 M) and DNMT3b (maximum inhibition 57%). In contrast, the inhibitory activity of Ferulic acid, a metabolite of -Oryzanol, ismuch lower than that of -Oryzanol. Furthermore, -Oryzanol acts as a partial antagonist against ERR,which primarily serves as a positive regulator for DNMT1 production, and con

5、sequently decreased theactivity of DNMT1 1.体内研究 The brown rice-specific bioactive component -Oryzanol, a mixture of ferulic acid ester and severalphytosterols, attenuates the preference for dietary fat via a decrease in hypothalamic endoplasmic reticulum(ER) stress. -Oryzanol ameliorates HFD-induced

6、 DNA hypermethylation of the promoter region of D2R inthe striatum of mice. -Oryzanol might regulate levels of DNMTs in a striatum-specific manner. -Oryzanolpartially decreases ERR activity (an approximately 40% reduction of the innate value). Oral administration of-Oryzanol to male mice by gavage s

7、ignificantly attenuates the preference for an HFD (93% of the values forvehicle-treated mice), resulting in an apparent attenuation of body weight gain 1.PROTOCOLKinase Assay 1 To assess the inhibitory activity of each compound on DNA methylation, the formation of S-adenosyl-l-homocysteine (SAH) is

8、measured in the presence of each compound (20 M for screening assays),S-adenosyl methionine (SAM; 10 M) and DNMT substrate (4 ng/L) at 37C for 90 min. To evaluate theMichaelis-Menten kinetics, DNMT1 (20 M) is incubated with -Oryzanol, SAM (5 M) and the indicatedconcentration of poly dI-dC at 37C for

9、 90 min. DNMT3a (100 M) and DNMT3b (100 M) are incubated with-Oryzanol, SAM (5 M) and the indicated concentration of poly dGdC at 37C for 120 min. The assays areperformed in quadruplicate. Extracted protein (0.75 mg/mL) is incubated with SAM (5 M), poly dI-dC (5 g/mL), and poly dGdC (5 g/mL) at 40C

10、for 120 min, and SAH formation is measured 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 Seven-week-old male C57BL/6J mice are used. To evaluate the preference for the HFD, -Oryzanol isadministrated to 8-week-old mice b

11、y gavage during the food choice test. For the other experiments, an HFDcontaining 0.4% -Oryzanol is manufactured as pellets. After 12 weeks of feeding, tissue is collected from thestriatum and hypothalamus. The daily intake of -Oryzanol, estimated from the mean food intake of the mice,is approximate

12、ly 320 g/g body weight. The doses of -Oryzanol are determined.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Kozuka C, et al. Impact of brown rice-specific -oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice. Diabetologia. 2017 Aug;60(8):1502-1511.McePdfHeightCaut