GSK3 Inhibitor XIII
(Synonyms: Glycogen Synthase Kinase 3 Inhibitor XIII) 目录号 : GC43790An inhibitor of GSK3
Cas No.:404828-08-6
Sample solution is provided at 25 µL, 10mM.
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GSK3 Inhibitor XIII is an aminopyrazole ATP-competitive inhibitor of glycogen synthase kinase 3 (GSK3), with 34% inhibition when used at a concentration of 2.5 µM. It inhibits androgen receptor transactivation in 22Rv1, LNCaP, and LNCaP-SSR cell lines in a dose-dependent manner. It promotes nuclear export of the androgen receptor and decreases translocation to the nucleus in PC3 and PCa prostate cancer cells, respectively. In HEK293 cells expressing the rat Nav1.2 channel, pretreatment with GSK3 inhibitor XIII dose-dependently potentiates peak current densities.
Cas No. | 404828-08-6 | SDF | |
别名 | Glycogen Synthase Kinase 3 Inhibitor XIII | ||
Canonical SMILES | CC1=CC(NC2=NC(C3=CC=CC=C3)=NC4=C2CCCC4)=NN1 | ||
分子式 | C18H19N5 | 分子量 | 305.4 |
溶解度 | DMF: 0.25 mg/ml,DMSO: 0.15 mg/ml | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 3.2744 mL | 16.372 mL | 32.7439 mL |
5 mM | 0.6549 mL | 3.2744 mL | 6.5488 mL |
10 mM | 0.3274 mL | 1.6372 mL | 3.2744 mL |
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The Nav1.2 channel is regulated by GSK3
Biochim Biophys Acta 2015 Apr;1850(4):832-44.PMID:25615535DOI:10.1016/j.bbagen.2015.01.011.
Background: Phosphorylation plays an essential role in regulating voltage-gated sodium (Na(v)) channels and excitability. Yet, a surprisingly limited number of kinases have been identified as regulators of Na(v) channels. We posited that glycogen synthase kinase 3 (GSK3), a critical kinase found associated with numerous brain disorders, might directly regulate neuronal Na(v) channels. Methods: We used patch-clamp electrophysiology to record sodium currents from Na(v)1.2 channels stably expressed in HEK-293 cells. mRNA and protein levels were quantified with RT-PCR, Western blot, or confocal microscopy, and in vitro phosphorylation and mass spectrometry to identify phosphorylated residues. Results: We found that exposure of cells to GSK3 Inhibitor XIII significantly potentiates the peak current density of Na(v)1.2, a phenotype reproduced by silencing GSK3 with siRNA. Contrarily, overexpression of GSK3β suppressed Na(v)1.2-encoded currents. Neither mRNA nor total protein expression was changed upon GSK3 inhibition. Cell surface labeling of CD4-chimeric constructs expressing intracellular domains of the Na(v)1.2 channel indicates that cell surface expression of CD4-Na(v)1.2 C-tail was up-regulated upon pharmacological inhibition of GSK3, resulting in an increase of surface puncta at the plasma membrane. Finally, using in vitro phosphorylation in combination with high resolution mass spectrometry, we further demonstrate that GSK3β phosphorylates T(1966) at the C-terminal tail of Na(v)1.2. Conclusion: These findings provide evidence for a new mechanism by which GSK3 modulates Na(v) channel function via its C-terminal tail. General significance: These findings provide fundamental knowledge in understanding signaling dysfunction common in several neuropsychiatric disorders.