S27-1047
S27-1047 is a brain-penetrant, potent and selective BChE (eqBChE IC50 = 7.16 nM; hBChE IC50 = 296.10 nM) inhibitor and Nrf2 activator. S27-1047 can directly bind Keap1, disrupt Keap1-Nrf2 interaction (FP IC50 = 36.87 nM), enhance antioxidant enzyme expression and activate the GSH-GPX4 axis to inhibit Aβ-induced ferroptosis. S27-1047 can protect against oxidative stress and neuroinflammation. S27-1047 can be used in Alzheimer's disease research.
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- CAS. Nr.: 3121876-09-0
- Formel: C25H16F2N8O3
- Molecular Weight:514.44
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Biologische Aktivität
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eqBCHE 7.16 nM (IC50) |
hBCHE 296.10 nM (IC50) |
GPX4 |
S27-1047 (10 μM; 0-24 h) can significantly upregulate the expression of Nrf2 downstream proteins in a time-dependent manner and the effect is more obvious in 5 to 10 h [1].
S27-1047 (10 μM; 0-24 h) shows low neurotoxicity in L02 cells , BV2 microglia cells and SH-SY5Y cells[1].
S27-1047 (1-20 μM; 6 h) can significantly increase the level of Nrf2 and its downstream protein (HO-1, NQO1 and GCLM) in a dose-dependent manner and induces a nearly 5-fold increasein Nrf2 protein expression at a concentration of 5 μM[1].
S27-1047 (10μM) exhibits antioxidant activity in an Nrf2-dependent manner[1].
S27-1047 (10 μM; 0-24 h) reveals significant nuclear accumulation of Nrf2 during 2-5 h treatment periods[1].
S27-1047 (10 μM; 2 h; 37-51 °C) induces a pronounced thermal stabilization of Keap1[1].
S27-1047 (10 μM) significantly promotes Keap1 degradation, consequently upregulating Nrf2 protein levels and effectively disrupting the Keap1-Nrf2 complexformation (FP IC50 = 36.87 nM)[1].
S27-1047 (1-20 μM; pretreatment for 2 h + co-incubation with Aβ1-42 for 24 h) demonstrates a potent, dose-dependent cytoprotective effect against H2O2-induced oxidative damage in L02 cells[1].
S27-1047 (1-20 μM; pretreatment for 2 h + co-incubation with Aβ1-42 for 24 h) demonstrates a dose-dependent cytoprotective effect against toxic Aβ fibril-induced cytotoxicity in the human neuroblastoma SH-SY5Y cells[1].
S27-1047 (10 μM; pretreatment for 24 h + co-incubation with Aβ1-42 for 24 h) significantly attenuats ROS generation without affecting cellular viability[1].
S27-1047 (10 μM) significantly inhibits the upregulation of tumor necrosis factor-alpha (TNF-α) in LPS-stimulated BV2 microglia cells[1].
S27-1047 (10 μM; pretreatment for 24 h + co-incubation with Aβ1-42 for 24 h) significantly attenuated lipid peroxidation in SH-SY5Y cells. S27-1047 robustly activates the System Xc- /GSH/GPX4 axis, a critical antioxidant pathway, leading to marked increases in GSH levels and GPX4 activity. S27-1047 can mitigate Aβ-induced ferroptosis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:L02 cells treated with H2O2 or Aβ 2
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Concentration:1 μM, 5 μM, 10 μM, 20 μM
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Incubation Time:24 h
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Result:Markedly alleviated oxidative damage in LO2 cells and demonstrated potent cytoprotective effects in a dose-dependent manner.
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Cell Line:SH-SY5Y cells
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Concentration:1 μM, 5 μM, 10 μM, 20 μM
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Incubation Time:24 h
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Result:Alleviated oxidative damage in SH-SY5Y cells and demonstrated potent cytoprotective effects in a dose-dependent manner.
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Cell Line:SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Increased levels of reduced lipid biomarkers.
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Cell Line:SH-SY5Y cells
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Concentration:10 μM
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Incubation Time:24 h
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Result:Increased in GSH levels and GPX4 activity.
S27-1047 (10 mg/kg; i.g.; one time) demonstrates the ability to cross the blood-brain barrier and exhibited moderate drug exposure levels within the brainin ICR mouse model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Mice wereinjected Aβ1-42 peptide (10 μg) icv injection on day 1[1]
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Dosage:1 mg/kg
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Administration:i.p.; once daily; days 3 to 16
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Result:Significantly improved cognitive impairment in mice and reversed deficits in spatial learning and working memory.
Demonstrated cognitive-enhancing efficacy superior not only to the positive control drug rivastigmine but also to equidoses of monotherapy (the BChE inhibitor S06-1064 or the Nrf2 activator 6) and the combination therapy of the two.
Upregulated the expression levels of Nrf2, the antioxidant-related protein GCLM, and the ferroptosis defense-related protein GPX4 in mouse brain tissue.
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Animal Model:ICR mouse model[1]
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Dosage:10 mg/kg
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Administration:i.g.; one time
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Result:Demonstrated the ability to successfully penetrate the blood-brain barrier and exhibit moderate drug exposure levels within the brain.
Chemical Information
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CAS. Nr. 3121876-09-0
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Molecular Weight 514.44
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Formel C25H16F2N8O3
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SMILES
O=C(NC1=CC=CC(C2=NOC(C3=CC=C(F)C=C3F)=N2)=C1)CN4C(C5=NON=C5N)=NC6=CC=CC=C46
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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