Potent and selective pan-With-No-Lysine (WNK) kinase inhibitor (IC50s: WNK1 = 5 nM, WNK2 = 1 nM, WNK3 = 6 nM, WNK4 = 9 nM), an important enzyme in blood pressure regulation and body fluid and electrolyte homeostasis.1 WNK kinases respond to hypertonicity by regulating SLC12 cation chloride transporters to rescue cell volume.2 WNK463 reduced migration of invasive types of breast cancer and attenuated tumor growth and metastatic burden in a mouse model.3 It induced a significant increase in NLRP3 inflammasome activation and pyroptosis specifically via WNK1 inhibition as well as increasing TNF production without inflammasome activation.4
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