AR-A014418

製品コードS7435 バッチS743502

印刷

化学情報

Chemical Structure Synonyms GSK-3β Inhibitor VIII Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C12H12N4O4S
分子量 308.31 CAS No. 487021-52-3
Solubility (25°C)* 体外 DMSO 61 mg/mL (197.85 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 AR-A014418 (GSK-3β Inhibitor VIII) is an ATP-competitive, and selective GSK3β inhibitor with IC50 and Ki of 104 nM and 38 nM in cell-free assays, without significant inhibition on 26 other kinases tested.
in vitro AR-A014418 inhibits tau phosphorylation at a GSK3-specific site (Ser-396) in 3T3 fibroblasts expressing human four-repeat tau protein with IC50 of 2.7 μM, and protects cultured N2A cells from death induced by blocking PI3K/PKB pathway. In hippocampal slices, AR-A014418 inhibits neurodegeneration mediated by beta-amyloid peptide. [1] While in NGP and SH-5Y-SY cells, AR-A014418 reduces neuroendocrine markers and suppresses neuroblastoma cell growth. [2]
in vivo In ALS mouse model with the G93A mutant human SOD1, AR-A014418 (0-4 mg/kg, i.p.) delays the onset of symptoms, improves motor activity, slows down disease progression, and postpons the endpoint of the disease. [3] In addition, AR-A014418 produces inhibition effect on acetic acid- and formalin-induced nociception in mice by modulating NMDA and metabotropic receptor signaling as well as TNF-α and IL-1β transmission in the spinal cord. [4]
特徴 Cell-permeable GSK3-selective inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ GSK3 Scintillation Proximity Assay
The competition experiments are carried out in duplicate with 10 concentrations of the inhibitor in clear-bottomed microtiter plates. The biotinylated peptide substrate, biotin-AAEELDSRAGS(PO3H2)PQL, is added at a final concentration of 2 μM in an assay buffer containing 6 milliunits of recombinant human GSK3 (equal mix of both α and β), 12 mM MOPS, pH 7.0, 0.3 mM EDTA, 0.01% β-mercaptoethanol, 0.004% Brij 35, 0.5% glycerol, and 0.5 μg of bovine serum albumin/25 μl and preincubated for 10-15 min. The reaction is initiated by the addition of 0.04 μCi of [γ-33P]ATP and unlabeled ATP in 50 mM Mg(Ac)2 to a final concentration of 1 μM ATP and assay volume of 25 μl. Blank controls without peptide substrate are used. After incubation for 20 min at room temperature, each reaction is terminated by the addition of 25 μl of stop solution containing 5 mM EDTA, 50 μM ATP, 0.1% Triton X-100, and 0.25 mg of streptavidin-coated SPA beads corresponding to ∼35 pmol of binding capacity. After 6 h the radioactivity is determined in a liquid scintillation counter. Inhibition curves are analyzed by non-linear regression using GraphPad Prism.
細胞アッセイ 細胞株 N2A cells
濃度 ~50 μM
反応時間 24 h
実験の流れ

Cell viability is assessed by calcein/propidium iodide uptake. Calcein AM is taken up and cleaved by esterases present within living cells, yielding yellowish-green fluorescence, whereas PI is only taken up by dead cells, which become orange-red fluorescent. In brief, N2A cells are cultured for 2 days in vitro and then treated with 50 μM LY-294002 in the presence of AR-A014418 or vehicle (DMSO) for 24 h. Subsequently, N2A cells are incubated for 30 min with 2 μM PI and 1 μM calcein-AM. The cultures are then rinsed three times with Hanks' buffered saline solution containing 2 mM CaCl2, and the cells are visualized by fluorescence microscopy using a Zeiss Axiovert 135 microscope. Three fields (selected at random) are analyzed per well (∼300 cells/field) in at least three different experiments. Cell death is expressed as percentage of PI-positive cells from the total number of cells. In every experiment, specific cell death is obtained after subtracting the number of dead cells present in vehicle-treated cultures.
動物実験 動物モデル ALS mouse model with the G93A mutant human SOD1
投薬量 ~4 mg/kg
投与方法 i.p.

カスタマーフィードバック

Data from [Data independently produced by , , Cell Physiol Biochem, 2017, 42(3):1177-1191]

Data from [Data independently produced by , , Biochem Biophys Res Commun, 2018, 503(4):3100-3107]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
Discovery of Novel Tacrine-Pyrimidone Hybrids as Potent Dual AChE/GSK-3 Inhibitors for the Treatment of Alzheimer's Disease [ J Med Chem, 2021, 64(11):7483-7506] PubMed: 34024109
Caspase-9 acts as a regulator of necroptotic cell death [ FEBS J, 2021, 10.1111/febs.15898] PubMed: 33899329
SOX2 enhances cell survival and induces resistance to apoptosis under serum starvation conditions through the AKT/GSK-3β signaling pathway in esophageal squamous cell carcinoma [ Oncol Lett, 2021, 21(4):269] PubMed: 33717266
Ribosomal S6 protein kinase 4 promotes radioresistance in esophageal squamous cell carcinoma [ J Clin Invest, 2020, 130(8):4301-4319] PubMed: 32396532
Suppression of histone deacetylases by SAHA relieves bone cancer pain in rats via inhibiting activation of glial cells in spinal dorsal horn and dorsal root ganglia. [ J Neuroinflammation, 2020, 22;17(1):125] PubMed: 32321538
Differences in the Sensitivity of Classically and Alternatively Activated Macrophages to TAK1 Inhibitor-Induced Necroptosis [ Cancer Immunol Immunother, 2020, 29] PubMed: 32472370
Resveratrol targets PD-L1 glycosylation and dimerization to enhance antitumor T-cell immunity. [ Aging (Albany NY), 2020, 12(1):8-34] PubMed: 31901900
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922
Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis. [ Cancer Cell, 2019, 35(5):798-815] PubMed: 31031016

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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