| Identification | Back Directory | [Name]
2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide | [CAS]
304896-28-4 | [Synonyms]
AGK2
CS-2248
AGK2;AGK-2;AGK 2
SIRT2 Inhibitor, AGK2
SIRT2 Inhibitor, AGK2 - CAS 304896-28-4 - Calbiochem
2-Cyano-3-(5-(2,5-dichlorophenyl)furan-2-yl)-N-(quinolin-5-yl)acrylamide
2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide
2-Propenamide, 2-cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-
2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide USP/EP/BP | [Molecular Formula]
C23H13Cl2N3O2 | [MDL Number]
MFCD01909444 | [MOL File]
304896-28-4.mol | [Molecular Weight]
434.27 |
| Chemical Properties | Back Directory | [Boiling point ]
675.1±55.0 °C(Predicted) | [density ]
1.445±0.06 g/cm3(Predicted) | [storage temp. ]
Room temp | [solubility ]
DMSO: soluble2mg/mL, clear (warmed) | [form ]
Yellow solid | [pka]
8.87±0.43(Predicted) | [color ]
White to Yellow to Orange |
| Hazard Information | Back Directory | [Uses]
Potent, selective and cell permeable inhibitor of sirtuin 2 (SIRT2) (IC50=3.5μM). Rescues α-synuclein-mediated toxicity. Modifies inclusion morphology in a cellular model of Parkinson’s disease. Protects against dopaminergic cell death. Leads to an increase in acetylated tubulin. | [Definition]
ChEBI: 2-cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-(5-quinolinyl)-2-propenamide is a member of quinolines. | [Biological Activity]
Selective inhibitor of SIRT2 (IC 50 = 3.5 μ M). Displays no activity at SIRT1 and SIRT3 at concentrations up to 40 μ M. Reduces α -synuclein-mediated toxicity in in vitro and in vivo models of Parkinson's disease. | [Biochem/physiol Actions]
AGK2 is a SIRT2 inhibitor. AGK2 rescues dopamine neurons from α-synuclein toxicity in Parkinson′s disease models. IC50 for SIRT2 = 3.5 uM. AGK2 is >15-fold more selective for SIRT2 than SIRT1 and SIRT3. AGK2 may be the most selective SIRT2 inhibitor available. | [in vivo]
AGK2 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)[4]. | [IC 50]
SIRT2: 3.5 μM (IC50); SIRT1: 30 μM (IC50); SIRT3: 91 μM (IC50) | [References]
[1]. outeiro tf, kontopoulos e, altmann sm, et al. sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of parkinson's disease. science, 2007, 317(5837): 516-519.
[2]. scuderi c, stecca c, bronzuoli mr, et al. sirtuin modulators control reactive gliosis in an in vitro model of alzheimer's disease. front pharmacol, 2014, 5: 89.
[3]. rotili d, tarantino d, nebbioso a, et al. discovery of salermide-related sirtuin inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer stem cells. j med chem, 2012, 55(24): 10937-10947. |
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