WZ4003

製品コードS7317 バッチS731701

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

C₂₅H₂₉ClN₆O₃

分子量

496.99

CAS No.

1214265-58-3

Solubility (25°C)*

体外

DMSO

10 mg/mL (20.12 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	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O 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。	0.350mg/ml (0.70mM)	Taking the 1 mL working solution as an example, add 50 μL of 7 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil 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。	0.350mg/ml (0.70mM)	Taking the 1 mL working solution as an example, add 50 μL of 7 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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	WZ4003 is a highly specific NUAK kinase inhibitor with IC50 of 20 nM and 100 nM for NUAK1 and NUAK2 in cell-base assays, respectively, without significant inhibition on 139 other kinases.
in vitro	In HEK-293 cells expressing wild-type NUAK1, WZ4003 (3–10 μM) markedly suppresses NUAK1-mediated MYPT1 phosphorylation. Moreover, this compound (10 μM) inhibits MYPT1 Ser445 phosphorylation as well as cell migration, invasion and proliferation to a similar extent as knock out in MEFs or knock down in U2OS cells of NUAK1. ^[1] It also exhibits a high, specific affinity to the L858R/T790M mutant EGFR, while a significantly reduced cellular IC50 against T790M containing Ba/F3 cells. ^[2]

製品説明

WZ4003 is a highly specific NUAK kinase inhibitor with IC50 of 20 nM and 100 nM for NUAK1 and NUAK2 in cell-base assays, respectively, without significant inhibition on 139 other kinases.

in vitro

In HEK-293 cells expressing wild-type NUAK1, WZ4003 (3–10 μM) markedly suppresses NUAK1-mediated MYPT1 phosphorylation. Moreover, this compound (10 μM) inhibits MYPT1 Ser445 phosphorylation as well as cell migration, invasion and proliferation to a similar extent as knock out in MEFs or knock down in U2OS cells of NUAK1. ^[1] It also exhibits a high, specific affinity to the L858R/T790M mutant EGFR, while a significantly reduced cellular IC50 against T790M containing Ba/F3 cells. ^[2]

プロトコル(参考用のみ)

キナーゼアッセイ	IC50 determination
キナーゼアッセイ	Active GST–NUAK1, GST–NUAK1[A195T] and GST–NUAK2 enzymes are purified using glutathione–Sepharose from HEK-293 cell lysates 36–48 h following the transient transfection of pEBG2T mammalian constructs expressing N-terminal GSTtagged NUAK1, NUAK1[A195T] or NUAK2. For peptide kinase assays, 96-well plates are used, and each reaction is performed in triplicate. Each reaction is set up in a total volume of 50 μL containing 100 ng of NUAK1 (wild-type or A195T mutant) or NUAK2 in 50 mM Tris/HCl (pH 7.5), 0.1 mM EGTA, 10 mM magnesium acetate, 200 μM Sakamototide, 0.1 mM [γ -³²P]ATP (450–500 c.p.m./pmol) and the indicated concentrations of inhibitors dissolved in DMSO. After incubation for 30 min at 30°C, reactions are terminated by adding 25 mM (final) EDTA to chelate the magnesium. Then, 40 μL of the reaction mix is spotted on to P81 paper and immersed in 50 mM orthophosphoric acid. Samples are washed three times in 50 mM orthophosphoric acid followed by a single acetone rinse and air drying. The incorporation of [γ -³²P]ATP into Sakamototide is quantified by Cerenkov counting. The values are expressed as a percentage of the DMSO control. IC50 curves are developed and IC50 values are calculated using GraphPad Prism software.
細胞アッセイ	細胞株	U2OS cells, and MEFs
	濃度	~10 μM
	反応時間	5 days
	実験の流れ	Cell proliferation assays are carried out colorimetrically in 96-well plates using the CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay kit following the manufacturer’s protocol. Initially, 2000 cells per well are seeded for U2OS cells and 3000 cells per well are seeded for MEFs. The proliferation assays are carried out over 5 days in the presence or absence of 10 μM this compound.

参考

https://pubmed.ncbi.nlm.nih.gov/24171924/
https://pubmed.ncbi.nlm.nih.gov/20033049/

カスタマーフィードバック

: , , J Cell Mol Med, 2017, 21(7):1411-1419

: Data from [Data independently produced by , , Brain Behav Immun, 2018, 72:89-100]

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：

NUAK1 activates STAT5/GLI1/SOX2 signaling to enhance cancer cell expansion and drives chemoresistance in gastric cancer [ Cell Rep, 2024, 43(7):114446]	PubMed: 38996065
The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung [ Int J Mol Sci, 2024, 25(3):1411.]	PubMed: 38338691
The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells [ Int J Mol Sci, 2024, 25(3)1411]	PubMed: 38338691
Localized Inhibition of Protein Phosphatase 1 by NUAK1 Promotes Spliceosome Activity and Reveals a MYC-Sensitive Feedback Control of Transcription. [ Mol Cell, 2020, 77(6):1322-1339]	PubMed: 32006464
Dual targeting of NUAK1 and ULK1 using the multitargeted inhibitor MRT68921 exerts potent antitumor activities [ Cell Death Dis, 2020, 11(8):712]	PubMed: 32873786
Microglia-Derived Extracellular Vesicles Carrying miR-711 Alleviate Neurodegeneration in a Murine Alzheimer's Disease Model by Binding to Itpkb [ Front Cell Dev Biol, 2020, 8:566530]	PubMed: 33240878
Safflor yellow A protects vascular endothelial cells from ox-LDL-mediated damage [ J Recept Signal Transduct Res, 2020, 1-8]	PubMed: 33167774
WZ4003 sensitizes non-small cell lung cancer cells to gefitinib via inhibition of ARK5 and epithelial-to-mesenchymal transition [ Am J Transl Res, 2020, 12(11):7377-7385]	PubMed: 33312374
Endothelial HNF4α potentiates angiogenic dysfunction via enhancement of vascular endothelial growth factor resistance in T2DM. [ J Cell Biochem, 2019, 120(8):12989-13000]	PubMed: 30873661
An Ancient Chinese Herbal Decoction Containing Angelicae Sinensis Radix, Astragali Radix, Jujuba Fructus, and Zingiberis Rhizoma Recens Stimulates the Browning Conversion of White Adipocyte in Cultured 3T3-L1 Cells. [ Evid Based Complement Alternat Med, 2019, 2019:3648685]	PubMed: 31316571

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。