3-TYP - SIRT3 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemE3-TYPCat. No.: HY-108331CAS No.: 120241-79-4分式: CHN分量: 146.15作靶點(diǎn): Sirtuin作通路: Cell Cycle/DNA Damage; Epigenetics儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (684.23 mM; Need ul

2、trasonic)Ethanol : 16.67 mg/mL (114.06 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 6.8423 mL 34.2114 mL 68.4229 mL5 mM 1.3685 mL 6.8423 mL 13.6846 mL10 mM 0.6842 mL 3.4211 mL 6.8423 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加

3、助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 3.25 mg/mL (22.24 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 3.25 mg/mL (22.24 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 1

4、0% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 3.25 mg/mL (22.24 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 3-TYP種選擇性的 SIRT3 抑制劑，IC50 值為 16 nM, 對(duì) SIRT1 和 SIRT2 的選擇性強(qiáng)，IC50 值分別為 88nM 和 92 nM。IC50 & Target SIRT3 SIRT1 SIRT216 nM (IC50) 88 nM (IC50) 92 nM (IC50)體外研究 3-TY

5、P inhibits melatonin-enhanced SIRT3 activity but does not affect SIRT3 protein expression. 3-TYPpretreatment reverses the protective effects of melatonin on cadmium (Cd)-induced mitochondrial-derivedO2 production and autophagic cell death. 3-TYP significantly attenuates melatonin-induced increases i

6、ndeacetylated-SOD2 expression and SOD2 activity in HepG2 cells exposed to Cd 1.體內(nèi)研究 3-TYP (50 mg/kg, i.p.) does not significantly influence the LVEF, LVFS, infarct size, serum LDH levels,apoptosis, and oxidative stress compared with those of the Sham group. Moreover, 3-TYP has little effect ongp91ph

7、ox, Nrf2, NQO 1, Bax, Bcl-2, Caspase-3, and cleaved Caspase-3 expression levels, compared withthe Sham group. 3-TYP significantly decreases SIRT3 activity and increases the acetylation of SOD2compared with that in the control group, without influencing SIRT3 expression. 3-TYP attenuates thecardiopro

8、tective effects of melatonin by decreasing the LVEF and LVFS after 24 hour of reperfusion. 3-TYPalso increases the infarct size, serum LDH levels, and apoptotic ratio compared with those in the IR+Melgroup 2.PROTOCOLCell Assay 1 Cell viability is analyzed using Cell Counting Kit-8. Briefly, 1104 cel

9、ls are inoculated into 96-well plates. Afterbeing treated, 90 L of medium and 10 L of CCK-8 solution are added to each well. The cells are thenincubated at 37C for 2 h. After incubation, the absorption at 450 nm is measured using an Infinite M200Microplate Reader. The results are expressed as a perc

10、entage of the control. The cell death is alsoevaluated using the trypan blue assay. HepG2 cells are plated in the 6-well plates (5105 cells per well) andincubated for 24 h. After being treated with Cd or melatonin, the cells are detached with 300 L trypsin-EDTAsolution. The mixture of detached cells

11、 is centrifugated at 300 g for 5 min. Then, the residue is combined with800 L trypan blue solution and dispersed. After 3 min staining, cells are counted using an automated cellcounter. The dead cells are stained with the blue color. Cell mortality (%) is expressed as percentage of thedead cell numb

12、er/the total cell number.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal In brief, male C57BL/6 mice are anesthetized with 2% isoflurane, and myocardial ischemia is produced byAdministration 2 temporarily exteriorizing the heart via a left thorac

13、ic incision and placing a 6-0 silk suture slipknot around theleft anterior descending coronary artery. After 30 minutes of myocardial ischemia, the slipknot is released,and the myocardium is reperfused for 3 hour (for western blot analysis and oxidative stress measurement) or2/3 Master of Small Mole

14、cules 您邊的抑制劑師www.MedChemE24 hour (for cardiac function, apoptotic index and infarct size determination). Sham-operated mice undergothe same surgical procedures except the suture placed under the left coronary artery is not tied. Ten minutesbefore reperfusion, mice are randomized to receive either ve

15、hicle (1% ethanol) or melatonin (20 mg/kg) byintraperitoneal injection. C57BL/6 mice are randomly divided into the following groups: (i) Sham group: miceunderwent the sham operation and are treated with vehicle (1% ethanol); (ii) Mel group: mice are treated withmelatonin (20 mg/kg via intraperitonea

16、l injection); (iii) IR+V group: mice underwent the MI/R operation andare treated with vehicle (1% ethanol); (iv) IR+Mel group: mice underwent the MI/R operation and are treatedwith melatonin (20 mg/kg via intraperitoneal injection 10 minutes before reperfusion); (v) IR+Mel+3-TYPgroup: mice are pretr

17、eated with 3-TYP (3-TYP is intraperitoneally injected at a dose of 50 mg/kg every 2 daysfor a total of three doses prior to the MI/R surgery), subjected to the MI/R operation, and treated withmelatonin (20 mg/kg via intraperitoneal injection 10 minutes before reperfusion); and (vi) IR+3-TYP group:mi

18、ce are pretreated with 3-TYP and then subjected to the MI/R operation.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Physiol Biochem. 2017;44(6):2212-2227.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Pi H, et al. SIRT3-SOD2-mROS-dependent autophagy in cadmium-ind