Rostafuroxin

Rostafuroxin (PST2238) is potent, selective, orally active Na-K-ATPase inhibitor, displaces 3H ouabain from dog kidney Na+, K+-ATPase with IC50 of 1.5 nM; displays excellent selectivity over a panel of general and hormonal receptors, with exception of thromboxane A2 receptor (61% inhibition at 1 uM) ; abolishes ouabain-dependent increase in the Na-K pump rate in cultured renal cells, abolishes the increase in blood pressure and renal Na-K ATPase activity caused by ouabain in rats model of hypertension.Hypertension Phase 2 Clinical (In Vitro) :Rostafuroxin (PST 2238) competitively inhibits Ouabain (HY-B0542) binding and signaling. Rostafuroxin antagonizes the molecularand functional effects of Ouabain by reversing the ouabain-induced, Src-dependent Na+, K+-ATPase phosphorylation and activation.Rostafuroxin (0.125-128 μM; for 24 h post treatment) has less than 20% reduction in cell viability in A549 cells and HSAEC. Rostafuroxin inhibits the expression of RSV-GFP in HSAEC (IC50=1.8 μM) and A549 cells (IC50=14.8 μM) .Rostafuroxin displaced [3H]Ouabain from the dog kidney Na+, K+-ATPase receptor (IC50=1.5 nM), is devoid of cardiac inotropic activity in isolated guinea pig atria, and shows no affinity up to 10-4 M with general (R1, R2, a1, a2, A1, A2, M1, M2, H1, H2, 5-HT1, 5-HT2, Ca2+ channels, TXA2/PGH2, PAF, GABAA, GABAB, DA-NE-5-HT uptake, glutammate, glycine, benzodiazepine) and hormonal (estrogenic, progestinic, androgenic, mineralcorticoid) receptors. (In Vivo) :Rostafuroxin (PST 2238; 1 mg/kg/day; gavage; for 3 weeks) decreases SBP and improves acetylcholine-induced relaxation.