WNK463，5MG，SML2809-5MG，Sigma

Biochem/physiol Actions

Orally active, highly selective & potent ATP-competitive inhibitor against with-No-Lysine (K) kinases WNK1-4 with in vivo efficacy in rodent models of hypertension.
WNK463 is a high-affinity, ATP-competitive inhibitor against with-No-Lysine (K) kinases (hWNK1/3/4 IC₅₀ = 5/6/9 nM with MBP & 1 μM ATP, hWNK2 IC₅₀ = 1 nM with MBP & 2 μM ATP, hWNK1 IC₅₀ = 41 nM with OSR1 & 0.5 μM ATP; hWNK1/4 KD = 3.71/3.84 by SPR), exhibiting weak affinity against only two other human kinases among a panel of 442. WNK463 downregulates the overexpressed OSR1 phosphorylation level in HEK293 cells (IC₅₀ = 106 nM; 1 hr) and displays in vivo efficacy in rodent hypertension models (1-10 mg/kg in rats p.o., 10 mg/kg in hWNK1 transgenic mice p.o.) with good orally availability (F = 100%/mice & 74%/rats post 1.5 mg/kg p.o.).