二氮嗪作用機制 - Medchemexpress - MCE中國

1、Product Data SheetDiazoxideCat. No.: HY-B1140CAS No.: 364-98-7分式: CHClNOS分量: 230.67作靶點: Potassium Channel; Autophagy作通路: Membrane Transporter/Ion Channel; Autophagy儲存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數(shù)據(jù)體外實驗 DMSO : 35 mg/mL (151.73 mM)H2O : 0

2、.1 mg/mL (insoluble)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 4.3352 mL 21.6760 mL 43.3520 mL5 mM 0.8670 mL 4.3352 mL 8.6704 mL10 mM 0.4335 mL 2.1676 mL 4.3352 mL請根據(jù)產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 mo

3、nth (protect from light)。-80C 儲存時，請在 6 個內使，-20C 儲存時，請在 1 個內使。體內實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubil

4、ity: 2.67 mg/mL (11.57 mM); Clear solution此案可獲得 2.67 mg/mL (11.57 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 26.7 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.67 mg/mL (11.57 mM); Clear solution此案可獲得 2.67 mg/mL (11.

5、57 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 26.7 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Diazoxide (Sch-6783)。種 ATP 敏感性的鉀離通道 (potassium channel) 激活劑，有潛于胰島素癥的研究體外研究 Diazoxide (Sch-6783) has a number of physiological effects, including lowering th

6、e blood pressure and rectifyinghypoglycemia. Diazoxide has powerful protective properties against cardiac ischemia1.Diazoxide (Sch-6783) could protect NSC-34 neurons against the main sources of neurodegenerative damage.Diazoxide increases Nrf2 nuclear translocation in NSC-34 motoneurons and prevents

7、 endogenous oxidative damage2.體內研究 Diazoxide (Sch-6783) attenuates postresuscitation brain injury, protects mitochondrial function, inhibits brain cellapoptosis, and activates the PKC pathway by opening mitoKATP channels3.Treatment with Diazoxide (Sch-6783) in wild-type mice decreases intraocular pr

8、essure (IOP) by 21.53.2% with anabsolute IOP reduction of 3.9 0.6 mm Hg4.PROTOCOLCell Assay 2 Diazoxide is dissolved in DMSO to prepare 50 mM stock solution. NSC-34 cells are allowed to differentiate for 8weeks under reduced serum conditions and then seeded in 24-well plates. Glutamate is dissolved

9、in culture mediumand added to cultures at concentration of 10 M for 24 h. Cell treatment with 100 M diazoxide starts 2 h beforeglutamate exposure. Cell viability is measured by the MTT assay2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats:

10、Adult male Sprague-Dawley rats with induced cerebral ischemia (n=10 per group) receive an intraperitonealAdministration 34 injection of 0.1% DMSO (1 mL; vehicle group), diazoxide (10 mg/kg; DZ group), or diazoxide (10 mg/kg) plus 5-hydroxydecanoate (5 mg/kg; DZ + 5-HD group) 30 min after CPR. The co

11、ntrol group (sham group, n=5) undergoessham operation, without cardiac arrest. Mitochondrial respiratory control rate (RCR) is determined. Brain cellapoptosis is assessed using TUNEL staining. Expression of Bcl-2, Bax, and protein kinase C epsilon (PKC) in thecerebral cortex is determined by Western

12、 blotting and immunohistochemistry3.Mouse: Diazoxide is prepared by diluting a 100 mM stock solution in 10% polyethoxylated castor oil in PBS. InC57BL/6 wild-type and Kir6.2(/) mice, a 5 L drop of 5 mM diazoxide is topically administered to one eye of eachmouse while the fellow control eye received

13、vehicle (DMSO and 10% polyethoxylated castor oil in the sameproportion as the treated eye). IOP is measured daily at 1 hour, 4 hours, and 23 hours following treatment. Treatmentwith diazoxide and vehicle is continued daily for 14 consecutive days4.MCE has not independently confirmed the accuracy of

14、these methods. They are for reference only.戶使本產品發(fā)表的科研獻 Cell Biol Int. 2020 Mar 3.See more customer validations on HYPERLINK www.MedChemE www.MedChemEPage 2 of 3 www.MedChemEREFERENCES1. Coetzee WA, et al. Multiplicity of effectors of the cardioprotective agent, diazoxide. Pharmacol Ther. 2013 Nov;14

15、0(2):167-75.2. Virgili N, et al. K(ATP) channel opener diazoxide prevents neurodegeneration: a new mechanism of action viaantioxidative pathway activation. PLoS One.2013 Sep 11;8(9):e75189.3. Wu H, et al. Diazoxide Attenuates Postresuscitation Brain Injury in a Rat Model of Asphyxial Cardiac Arrest by Opening Mitochondrial ATP-SensitivePotassium Channels. Biomed Res Int. 2016;2016:1253842.4. Chowdhury UR, et al. ATP-sensitive potassium (K(ATP) channel openers diazoxide and nicorandil lower intraocular pressure in vivo. Invest OphthalmolVis Sci. 2013 Jul