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      AGK2
      AGK2

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      This product is for research use only, not for human use. We do not sell to patients.
      Number： - + Pieces（InventoryPieces）
      InvivoChem Cat #: V0436
      CAS #: 304896-28-4Purity ≥98%

      Description: AGK2 is a novel, potent, and selective inhibitor of SIRT2 (sirtuin 2, histone deacetylase) with potential anti-inflammatory activity. As a cell-permeable epigenetic modifier, AGK2 inhibits SIRT2 with an IC50 value of 3.5 μM and showed little effects on SIRT1 and 3 at concentrations of over 40 μM. AGK 2 increased the level of acetylated tubulin heterodimers in bovine brain. In primary rat astrocytes, AGK-2 (35 μM) significantly inhibited astrocyte viability and proliferation and also inhibited astrocyte activation induced by beta amyloid 1-42 (Aβ 1-42).

      References: Science. 2007 Jul 27;317(5837):516-9; Biochem Biophys Res Commun. 2012 Jan 6;417(1):468-72; Oncotarget. 2013 Dec;4(12):2354-65.

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      Molecular Weight (MW)434.27
      FormulaC23H13Cl2N3O2
      CAS No.304896-28-4
      Storage-20℃ for 3 years in powder form
      -80℃ for 2 years in solvent
      Solubility (In vitro)DMSO: 10 mg/mL (23.0 mM)          
      Water: <1 mg/mL
      Ethanol: <1 mg/mL
      Solubility (In vivo) 8% DMSO+30% PEG 300+ddH2O: ~1.5 mg/mL
      Synonyms

      Synonym: AGK-2; AGK-2; AGK-2.

      Chemical Name: 2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide

      InChi Key: SVENPFFEMUOOGK-SDNWHVSQSA-N

      InChi Code: InChI=1S/C23H13Cl2N3O2/c24-15-6-8-19(25)18(12-15)22-9-7-16(30-22)11-14(13-26)23(29)28-21-5-1-4-20-17(21)3-2-10-27-20/h1-12H,(H,28,29)/b14-11+

      SMILES Code: O=C(NC1=C2C=CC=NC2=CC=C1)/C(C#N)=C/C3=CC=C(C4=CC(Cl)=CC=C4Cl)O3


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      In Vitro

      In vitro activity: In SIRT2-myc-expressing HeLa cells, AGK2 effectively inhibits the activity of SIRT2, and increases acetylated tubulin. AGK2 protects dopaminergic neurons from α-Syn–induced toxicity in primary midbrain cultures. AGK2 induces both necrosis and caspase-3-dependent apoptosis in C6 glioma cells. SIRT2 also decreases merlin-mutant viability of mouse schwann cells (MSCs) without substantially reducing wild-type MSC viability.

      Cell Assay: 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 37°C in a 5% CO2 incubator for 10-15 days, and the cell colonies are scored using an inverted microscope

      In VivoAGK2 significantly reduces mortality and decreases levels of cytokines in blood (TNF-α: 298.3±24.6 vs 26.8±2.8 pg/mL, p=0.0034; IL-6: 633.4±82.8 vs 232.6±133.0 pg/mL, p=0.0344) and peritoneal fluid (IL-6: 704.8±67.7 vs 391.4±98.5 pg/mL, p=0.033) compare to vehicle control. AGK2 also suppresses the TNF-α and IL-6 production in the culturing splenocytes (TNF-α: 68.1±6.4 vs 23.9±2.8 pg/mL, p=0.0009; IL-6: 73.1±4.2 vs 49.6±3.0 pg/mL; p=0.0051)
      Animal modelMice are intraperitoneally given either AGK2 (82 mg/kg) in dimethyl sulfoxide (DMSO) or DMSO alone, and 2 h later subjects to CLP. Survival is monitored for 240 hours. AGK2-treating mice are grouped into (i) DMSO vehicle, and (ii) AGK2, with sham mice (operating but without any treatment) serving as controls. Peritoneal fluid and peripheral blood are examined at 24 and 48 hours for cytokine production
      Formulation & Dosage82 mg/kg; i.p.
      References

       Science. 2007 Jul 27;317(5837):516-9; Oncotarget. 2013 Dec;4(12):2354-65.; Curr Mol Med. 2015;15(7):634-41.

      These protocols are for reference only. InvivoChem does not independently validate these methods.

      AGK2
      SIRT2 Inhibition Causes Release of LDH and HMGB1 from Merlin-Mutant MSC. Oncotarget. 2013 Dec; 4(12): 2354–2365.

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