Rostafuroxin

Rostafuroxin (PST 2238), a digitoxigenin derivative, is an orally active and potent Na⁺,K⁺-ATPase (ATP1A1) antognist. Rostafuroxin binds specifically to the ATP1A1 extracellular domain and blocks respiratory syncytial virus (RSV)-triggered EGFR Tyr845 phosphorylation. Rostafuroxin has antihypertensive and anti-RSV activity^[1][2][3][4]. 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^[3][4].
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)^[3].
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^[1].
In Vivo: Rostafuroxin (PST 2238; 1 mg/kg/day; gavage; for 3 weeks) decreases SBP and improves acetylcholine-induced relaxation^[4].