| Identification | Back Directory | [Name]
WNK463 | [CAS]
2012607-27-9 | [Synonyms]
WNK463
CS-2515
WNK 463;WNK-463
1H-Imidazole-5-carboxamide, N-(1,1-dimethylethyl)-1-[1-[5-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]-2-pyridinyl]-4-piperidinyl]- | [Molecular Formula]
C21H24F3N7O2 | [MDL Number]
MFCD30489744 | [MOL File]
2012607-27-9.mol | [Molecular Weight]
463.46 |
| Chemical Properties | Back Directory | [density ]
1.43±0.1 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
DMSO : ≥ 30 mg/mL (64.73 mM) | [form ]
Solid | [pka]
15.18±0.46(Predicted) | [color ]
White to off-white | [InChI]
1S/C21H24F3N7O2/c1-20(2,3)27-17(32)15-11-25-12-31(15)14-6-8-30(9-7-14)16-5-4-13(10-26-16)18-28-29-19(33-18)21(22,23)24/h4-5,10-12,14H,6-9H2,1-3H3,(H,27,32) | [InChIKey]
HWSHOMMVLGBIDN-UHFFFAOYSA-N | [SMILES]
C1N(C2CCN(C3=NC=C(C4=NN=C(C(F)(F)F)O4)C=C3)CC2)C(C(NC(C)(C)C)=O)=CN=1 |
| Hazard Information | Back Directory | [Uses]
WNK 463, is a pan-WNK kinase inhibitor, acting on WNK1, WNK2, WNK3, and WNK4 kinases. It has shown to affect blood pressure, heart rate, body fluid and electrolyte homeostasis in rodent models of hypertension. | [Biochem/physiol Actions]
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.). | [in vivo]
WNK463 (1-10 mg/kg; oral administration; 4 hours; Spontaneously hypertensive Sprague Dawley rats) treatment produces dose-dependent decreases in blood pressure and simultaneous increases in heart rate in conscious SHRs. WNK463 produces significant and dose-dependent increases in urine output as well as urinary sodium and potassium excretion rates.
WNK463 is orally bioavailable in Sprague Dawley rats with a half-life of 2.1 hours[1]. | Animal Model: | Spontaneously hypertensive Sprague Dawley rats (34-42 weeks of age) [1] | | Dosage: | 1 mg/kg, 3 mg/kg, or 10 mg/kg (Pharmacokinetic study) | | Administration: | Oral administration; 4 hours | | Result: | Decreased in blood pressure and simultaneous increases in heart rate. WNK463 produced significant and dose-dependent increased in urine output as well as urinary sodium and potassium excretion rates.
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| [IC 50]
WNK2: 1 nM (IC50); WNK3: 6 nM (IC50); WNK4: 9 nM (IC50); WNK1: 5 nM (IC50) | [storage]
Store at -20°C |
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