Allosteric inhibition of recombinant human N-terminal GST-tagged WNK1 catalytic domain (1 to 491 residues) expressed in baculovirus expression system using fluorescein-labeled OSR1 peptide as substrate after 3 hrs by HTRF assay
Allosteric inhibition of WNK1 (unknown origin) expressed in HEK293 cells co-expressing flag-OSR1 assessed as reduction in sorbitol-stimulated OSR1 phosphorylation preincubated with compound for 2.5 hrs followed co-administration with sorbitol measured after 1 hr by AlphaLISA assay
Anti-hypertensive activity in po dosed human WNK1 transgenic FVB mouse assessed as reduction in blood pressure administered via gavage measured every 10 minutes for 15 seconds after 6 to 12 hrs
Anti-hypertensive activity in human WNK1 transgenic FVB mouse assessed plasma concentration required for SBP reducing activity at 30 mg/kg, po via gavage measured after 7 hrs
Anti-hypertensive activity in SHR rat assessed as induction of diuresis administered orally as single dose on day 2,3 and 4 measured for 7 hrs post dose
Anti-hypertensive activity in SRH rat assessed as induction of natriuresis administered orally as single dose on day 2,3 and 4 measured for 7 hrs post dose
Anti-hypertensive activity in SRH rat assessed as induction of kaliuresis administered orally as single dose on day 2,3 and 4 measured for 7 hrs post dose
Anti-hypertensive activity in po dosed human WNK1 transgenic FVB mouse assessed as reduction in blood pressure administered via gavage measured every 10 minutes for 15 seconds after 2 hrs