AGK2 - Sirtuin 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAGK2Cat. No.: HY-100578CAS No.: 304896-28-4分式: CHClNO分量: 434.27作靶点: Sirtuin作通路: Cell Cycle/DNA Damage; 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 : 6 mg/mL (13.82 mM; Need ult

2、rasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液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，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储

3、备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 0.5 mg/mL (1.15 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.5 mg/mL (1.15 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 0.5 mg/mL (

4、1.15 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 AGK2个选择性 SIRT2 抑制剂，其 IC50 值为 3.5 M。AGK2 也可以抑制 SIRT1 和 SIRT3，且IC50 值分别为 30 和 91 M。IC50 & Target SIRT2 SIRT1 SIRT33.5 M (IC50) 30 M (IC50) 91 M (IC50)体外研究 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.体内研究 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.户使本产品发表的科研献 Acta Phar

12、m Sin B. 2019 Jun.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您边的抑制剂师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.