AGK2 - Sirtuin 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAGK2Cat. No.: HY-100578CAS No.: 304896-28-4分式: CHClNO分量: 434.27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 : 6 mg/mL (13.82 mM; Need ult

2、rasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.3027 mL 11.5136 mL 23.0271 mL5 mM 0.4605 mL 2.3027 mL 4.6054 mL10 mM 0.2303 mL 1.1514 mL 2.3027 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)

3、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: 0.5 mg/mL (1.15 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.5 mg/mL (1.15 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.5 mg/mL (

4、1.15 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 AGK2個(gè)選擇性 SIRT2 抑制劑，其 IC50 值為 3.5 M。AGK2 也可以抑制 SIRT1 和 SIRT3，且IC50 值分別為 30 和 91 M。IC50 & Target SIRT2 SIRT1 SIRT33.5 M (IC50) 30 M (IC50) 91 M (IC50)體外研究 AGK2 significantly inhibits cell proliferation in a

5、 dose-dependent manner. AGK2 also significantly inhibits cellgrowth in a dose-dependent manner without inducing cytotoxicity at low doses. Twelve days after AGK2 (5 M) treatment, cells show a significantly reducing colony forming ability in soft agar to 46% of the control cells.Western blot analysis

6、 shows that the levels of CDK4 or CDK6 and cyclin D1 are decreased after AGK2treatment in a dose-dependent manner. In addition, AGK2 inhibits the expression of p53 protein 2.Treatment of microglial BV2 cells with 10 M AGK2 leads to a significant increase in PAR signals. Treatmentof microglial BV2 ce

7、lls with 10 M AGK2 also leads to a significant decrease in the intracellular ATP andsignificant increases in both late-stage apoptosis and necrosis of the cells 3.體內(nèi)研究 AGK2 significantly reduces mortality and decreases levels of cytokines in blood (TNF-: 298.324.6 vs26.82.8 pg/mL, p=0.0034; IL-6: 63

8、3.482.8 vs 232.6133.0 pg/mL, p=0.0344) and peritoneal fluid (IL-6:704.867.7 vs 391.498.5 pg/mL, p=0.033) compare to vehicle control. AGK2 also suppresses the TNF-and IL-6 production in the culturing splenocytes (TNF-: 68.16.4 vs 23.92.8 pg/mL, p=0.0009; IL-6:73.14.2 vs 49.63.0 pg/mL; p=0.0051) 4.PRO

9、TOCOLCell Assay 2 Cells are exposed to different concentrations of AGK2 in 1 mL of 0.3% basal medium agar containing 10%FBS. The cultures are maintained at 37C in a 5% CO2 incubator for 10-15 days, and the cell colonies arescored using an inverted microscope 2.MCE has not independently confirmed the

10、 accuracy of these methods. They are for reference only.Animal Mice are intraperitoneally given either AGK2 (82 mg/kg) in dimethyl sulfoxide (DMSO) or DMSO alone, and 2Administration 4 h later subjects to CLP. Survival is monitored for 240 hours. AGK2-treating mice are grouped into (i) DMSOvehicle,

11、and (ii) AGK2, with sham mice (operating but without any treatment) serving as controls. Peritonealfluid and peripheral blood are examined at 24 and 48 hours for cytokine production 4.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) Acta Phar

12、m Sin B. 2019 Jun.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Tatum PR, et al. Identification of novel SIRT2-selective inhibitors using a click chemistry approach. Bioorg Med Chem Lett. 2014 Apr15;24(8):1871-4.2. Kim HW, et a

13、l. Sirtuin inhibitors, EX527 and AGK2, suppress cell migration by inhibiting HSF1 protein stability. Oncol Rep. 2016Jan;35(1):235-42.3. Li Y, et al. Poly(ADP-ribose) polymerase mediates both cell death and ATP decreases in SIRT2 inhibitor AGK2-treated microglial BV2cells. Neurosci Lett. 2013 Jun 7;544:36-40.4. Zhao T, et al. Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model. Curr Mol Med. 2015;15(7):634-41.