WNK463

製品コードS8358 バッチS835802

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

C₂₁H₂₄F₃N₇O₂

分子量

463.46

CAS No.

2012607-27-9

Solubility (25°C)*

体外

DMSO

92 mg/mL (198.5 mM)

Ethanol

92 mg/mL (198.5 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

5%DMSO 1 30%PEG300 2 5%Tween80 3 60%ddH2O

8.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 160 mg/ml clarified DMSO stock solution to 300 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 600 μL of ddH2O to adjust the volume 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	WNK463 is a pan-WNK-kinase inhibitor. It potently inhibits the in vitro kinase activity of all four WNK family members (WNK1, WNK2, WNK3, and WNK4) with IC50 of 5nM, 1nM, 6nM, and 9nM.
in vitro	WNK463 potently inhibited the in vitro kinase activity of all four WNK family members (WNK1, WNK2, WNK3, and WNK4). WNK463 also inhibited WNK1-catalyzed phosphorylation of the native WNK substrate, oxidative stress response 1 (OSR1) in a biochemical assay and in human embryonic kidney 293 (HEK293) cells that express exogenous OSR1 and that are activated by sorbitol-mediated osmotic stress^[1].
in vivo	In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electrolyte homeostasis. WNK463 is orally bioavailable in C57BL/6 mice (100%) and Sprague Dawley rats (74%), with a half-life of 3.6 and 2.1 h, respectively. In spontaneously hypertensive rats (SHRs), WNK463 administered orally (p.o.) at 1, 3, or 10 mg per kg body weight (mg/kg) p.o. achieved maximum plasma concentration (Cmax) values of 88, 441, and 1,170 nM, respectively. These exposures produced dose-dependent decreases in blood pressure and simultaneous increases in heart rate in conscious SHRs. Moreover, WNK463 produced significant and dose-dependent increases in urine output as well as urinary sodium and potassium excretion rates. Orally administered WNK463 also significantly decreased blood pressure in these hypertensive mice. WNK463 elicited in vivo cardiovascular and renal effects through WNK kinase inhibition^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	HUVECs
	濃度	1 µM
	反応時間	6 h
	実験の流れ	Cells were treated with indicated concentration of drug for 6 h.
動物実験	動物モデル	Male Sprague Dawley rats or male C57BL/6 mice
	投薬量	1 mg/kg(i.v.) or 3 mg/kg (oral)
	投与方法	i.v. or oral administration

参考

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：

Isoform-independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells [ FASEB J, 2024, 38(7):e23604]	PubMed: 38591106
The WNK1-ERK5 route plays a pathophysiological role in ovarian cancer and limits therapeutic efficacy of trametinib [ Clin Transl Med, 2023, 13(4):e1217]	PubMed: 37029785
WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis [ Proc Natl Acad Sci U S A, 2022, 119(30):e2203743119]	PubMed: 35867836
Cancer genes disfavoring T cell immunity identified via integrated systems approach [ Cell Rep, 2022, 40(5):111153]	PubMed: 35926468
WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia [ Am J Respir Cell Mol Biol, 2022, 67(4):491-502]	PubMed: 35849656
Discovery of Small Molecule KCC2 Potentiators Which Attenuate In Vitro Seizure-Like Activity in Cultured Neurons [ Front Cell Dev Biol, 2022, 10:912812]	PubMed: 35813195
WNK1 Enhances Migration and Invasion in Breast Cancer Models [ Mol Cancer Ther, 2021, 20(10):1800-1808]	PubMed: 34253593
Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling. [ BMC Cancer, 2020, 20(1):4]	PubMed: 31898540
Is amiloride a promising cardiovascular medication to persist in the COVID-19 crisis [ Drug Discov Ther, 2020, 14(5):256-258]	PubMed: 33116037
Interpreting an apoptotic corpse as anti-inflammatory involves a chloride sensing pathway. [ Nat Cell Biol, 2019, 21(12):1532-1543]	PubMed: 31792382

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。