AZD1080

製品コードS7145 バッチS714502

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₉H₁₈N₄O₂

分子量

334.37

CAS No.

612487-72-6

Solubility (25°C)*

体外

DMSO

66 mg/mL (197.38 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	20.000mg/ml (59.81mM)	Taking the 1 mL working solution as an example, add 300 μL of clarified PEG400 stock solution of 66.67 mg/ml to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O Dilute to 1 mL. The mixed solution should be used immediately for optimal results.

* <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	AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with K_i of 6.9 nM and 31 nM, respectively, shows >14-fold selectivity against CDK2, CDK5, CDK1 and Erk2.
in vitro	AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a K_i of 6.9 nM and 31 nM, respectively, shows >14-fold selectivity against cdk2, cdk5, cdk1 and Erk2. This compound inhibits tau phosphorylation in cells expressing human tau, with IC50 of 324 nM. ^[1]
in vivo	AZD1080 inhibits tau phosphorylation in rat brain after oral administration, with brain/plasma exposure ratio of 0.5 – 0.8 at peak concentrations. This compound reverses cognitive deficits and rescues dysfunctional synapses in mice. Acute oral treatment with this chemical inhibits peripheral GSK3 activity, produces a dose-dependent reduction of the phosphorylated to total glycogen synthase (GS) ratio, with a mean maximal inhibitory effect of 49% at the highest dose (10 μmol/kg) at 2 h after dosing. ^[1]
特徴	A brain permeable GSK3 inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase Assay
キナーゼアッセイ	GSK3 scintillation proximity assay is done. The competition experiments are carried out in duplicate with 10 concentrations of this compound 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.
細胞アッセイ	細胞株	3T3 fibroblasts stably expressing 4-repeat human tau
	濃度	~20mM
	反応時間	0-8 h
	実験の流れ	3T3 fibroblasts are engineered to stably express four-repeat tau protein. These cells have high endogenous levels of GSK3 that is able to phosphorylate tau protein constitutively. This phosphorylation is inhibited by LiCl. After treatment with different compounds, cultures are washed twice with 5 mM MgCl₂-PBS. The samples are homogenized at 4 °C, and protein content is determined by Bradford method. Total protein (25 μg) is electrophoresed on 10% SDS-PAGE gel and transferred to a nitrocellulose membrane. The experiments are performed using the following primary antibodies: tau Ser(P)-396, 1:1000; Tau5, 1:1000; and anti-GSK3β, 1:1000. The filters are incubated with the antibody at 4 °C overnight in 5% nonfat dried milk. A secondary antibody (1:5000), followed by ECL detection reagents are used for immunodetection. Quantitation of immunoreactivity is performed by densitometric scanning.
動物実験	動物モデル	C57BL/6 mice
	投薬量	3 or 10 μmol/kg, 6 mL/kg
	投与方法	oral gavage

参考

https://pubmed.ncbi.nlm.nih.gov/23410232/

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：

Temporal activation of WNT/β-catenin signaling is sufficient to inhibit SOX10 expression and block melanoma growth. [ Oncogene, 2020, 39(20):4132-4154]	PubMed: 32238882
Small Molecule Inhibitors of DYRK1A Identified by Computational and Experimental Approaches [ Int J Mol Sci, 2020, 21(18)E6826]	PubMed: 32957634
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004]	PubMed: 31740922
GSK3 suppression upregulates β-catenin and c-Myc to abrogate KRas-dependent tumors. [ Nat Commun, 2018, 9(1):5154]	PubMed: 30514931
Pir2/Rnf144b is a potential endometrial cancer biomarker that promotes cell proliferation. [ Cell Death Dis, 2018, 9(5):504]	PubMed: 29724995
Beta-amyloid 1-42 monomers, but not oligomers, produce PHF-like conformation of Tau protein [ Aging Cell, 2016, 15(5):914-23]	PubMed: 27406053

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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