WNK463

SKU: orb1300140

Description

WNK463 is a potent and selective small-molecule inhibitor targeting all four WNK kinase isoforms (WNK1, WNK2, WNK3, and WNK4). It is a valuable research tool for investigating WNK signaling pathways in hypertension, renal physiology, and cancer, supporting both in vitro enzymatic assays and cellular studies.

Research Area

Cell Biology, Metabolism Research, Protein Biochemistry

Key Properties

• CAS Number: 2012607-27-9
• MW: 463.46
• Purity: ≥95%
• Formula: C₂₁H₂₄F₃N₇O₂
• SMILES: CC(C)(C)NC(=O)c1cncn1C1CCN(CC1)c1ccc(cn1)-c1nnc(o1)C(F)(F)F
• Target: Serine/threonin kinase,Serine Protease
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.12 mM);DMSO:85 mg/mL (183.4 mM);Ethanol:85 mg/mL (183.4 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  WNK2:1nM|WNK3:6nM|WNK4:9 nM|WNK1:5nM
• 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.
• 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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Inhibitor, WNK 463, WNK, WNK463, WNK-463, Serinekinase, threonin kinase, threoninkinase, Threonine proteases, Serine proteases, Serine endopeptidases, Ser/Thr Protease, Serine kinase

Compound Identifiers

PubChem CID

121487936