AR-A014418 Chemische Eigenschaften,Einsatz,Produktion Methoden
R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R37/38:Reizt die Atmungsorgane und die Haut.
R41:Gefahr ernster Augenschäden.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36/39:Bei der Arbeit geeignete Schutzkleidung und Schutzbrille/Gesichtsschutz tragen.
Chemische Eigenschaften
Pale Yellow Solid
Verwenden
AR-A014418 has been used as an inhibitor of glycogen synthase kinase 3 (GSK3).
Allgemeine Beschreibung
A cell-permeable thiazole-containing urea compound that acts as a potent inhibitor of GSK-3. Shown to inhibit GSK-3β with high potency (IC
50 = 104 nM). Inhibition is competitive with respect to ATP (K
i = 38 nM). Specificity has been reported using a panel of 28 different kinases, including Cdk2 and Cdk5 (IC
50 >100 μM). Shown to prevent tau phosphorylation at a GSK-3-specific site. Also shown to protect neuronal cells against Aβ-mediated neurodegeneration
in vitro and reduce tauopathy in mice
in vivo (30 μmol/kg delivered with 40% PEG400 and 40% dimethylacetamide in water). Caution: Do not use delivering vehicles containing dimethylamine for
in vivo studies, as it is highly toxic to animals. A 25 mM (5 mg/649 μl) solution of GSK-3β Inhibitor VIII (Cat. No.
361557) in DMSO is also available.
Enzyminhibitor
This ATP-competitive protein kinase inhibitor (FW = 308.31 g/mol; CAS 487021-52-3; Solubility: 62 mg/mL DMSO; <1 mg/mL H2O) selectively targets glycogen synthase kinase 3β (GSK3β),with IC50 = 104 nM; Ki = 38 nM. Attesting to its high specificity for GSK3, AR-A014418 does not significantly inhibit Cdk2 or Cdk5 (IC50 > 100 μM) or 26 other kinases. AR-A014418 inhibits phosphorylation of the microtubule-associated protein Tau at Ser-396 (i.e., the GSK3-specific site) in cells stably expressing human four-repeat Tau. AR-A014418 protects N2A neuroblastoma cells against cell death mediated by inhibition of the phosphatidylinositol 3-kinase/protein kinase B survival pathway. AR- A014418 inhibits neurodegeneration mediated by b-amyloid peptide in hippocampal slices. Treatment of neuroblastoma cell lines with AR- A014418 reduced the level of GSK-3α phosphorylation at Tyr-279 compared to GSK-3β phosphorylation at Tyr-216, and attenuated growth via the maintenance of apoptosis.. AR-A014418-dependent antinociceptive effects are induced by modulation of the glutamatergic system through metabotropic and ionotropic (NMDA) receptors and the inhibition of TNF-α and IL-1β cytokine signaling.
AR-A014418 Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
