[CAS NO. 156722-18-8] Rostafuroxin
PRODUCTS SPECIFICATIONS [156722-18-8]
DESCRIPTION [156722-18-8]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 374.51 |
| Molecular Formula | C23H34O4 |
| SMILES | O[C@]([C@@](CC[C@@]1([H])[C@@]2(CC[C@H](O)C1)C)([H])[C@]2([H])CC3)(CC[C@@]4(C5=COC=C5)O)[C@]34C |
Summary
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 (IC
50
=1.8 μM) and A549 cells (IC
50
=14.8 μM)
[3]
.
Rostafuroxin displaced [
3
H]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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Rostafuroxin (PST 2238; 1 mg/kg/day; gavage; for 3 weeks) decreases SBP and improves acetylcholine-induced relaxation
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male 7-week-old Wistar rats [4] |
| Dosage: | 1 mg/kg |
| Administration: | Gavage; daily; for 3 weeks |
| Result: | Decreased SBP, improved acetylcholine-induced relaxation via enhanced nitric oxide synthesis and bioavailability, decreased superoxide anion generation from NAD(P)H oxidase and cyclooxygenase-2 and reduced cytoplasmic tyrosine kinase Src phosphorylation. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03217825 | Windtree Therapeutics |
Hypertension
|
December 2015 | Phase 2 |
| NCT01320397 | RostaQuo S.p.A. |
Essential Hypertension
|
May 2011 | Phase 2 |
| NCT00415038 | sigma-tau i.f.r. S.p.A. |
Essential Hypertension
|
February 2005 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 50 mg/mL ( 133.51 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6702 mL | 13.3508 mL | 26.7016 mL |
| 5 mM | 0.5340 mL | 2.6702 mL | 5.3403 mL |
| 10 mM | 0.2670 mL | 1.3351 mL | 2.6702 mL |
References
- [1] Quadri L, et al. 17 beta-(3-furyl)-5 beta-androstane-3 beta, 14 beta, 17 alpha-triol (PST 2238). A very potent antihypertensive agent with a novel mechanism of action. J Med Chem. 1997 May 23;40(11):1561-4.
- [2] Ferrari P, et al. PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension. J Pharmacol Exp Ther. 1999 Mar;288(3):1074-83.
- [3] Matthias Lingemann, et al. The alpha-1 subunit of the Na ,K -ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells. PLoS Pathog. 2019 Aug 5;15(8):e1007963.
- [4] Camilla F Wenceslau, et al. Rostafuroxin ameliorates endothelial dysfunction and oxidative stress in resistance arteries from deoxycorticosterone acetate-salt hypertensive rats: the role of Na ,K -ATPase/cSRC pathway. J Hypertens. 20
Synonyms