生物活性

• 描述Rostafuroxin (PST 2238), a digitoxigenin derivative, is an orally active and potent Na+,K+-ATPase (ATP1A1) antognist^[3]. Rostafuroxin (PST 2238) is a new oral antihypertensive agent able to selectively antagonize EO, adducin pressor, and molecular effects. It is endowed with high potency and efficacy in reducing blood pressure and preventing organ hypertrophy in animal models representative of both adducin and EO mechanisms. In the vasculature, it normalizes the increased myogenic tone caused by nanomolar ouabain^[4]. The antihypertensive rostafuroxin suppresses Na(+) resorption and the Src-epidermal growth factor receptor-ERK pathway in kidney tubule cells^[5]. In A549 cells and HSAEC, RSV (Human respiratory syncytial virus) uptake could be inhibited by the cardiotonic steroid ouabain and the digitoxigenin derivative PST2238 (rostafuroxin) that bind specifically to the ATP1A1 extracellular domain and block RSV-triggered EGFR (epidermal growth factor receptor) Tyr845 phosphorylation^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00415038	Essential Hypertension	Phase 2	Completed	-	Belgium ... more >> Catholic University of Leuven - Laboratory of Hypertension, Dept. of Molecular and Cardiov. Research - Campus Gasthuisberg Leuven, Belgium, B-3000 Collapse <<
  NCT03217825	Hypertension	Phase 2	Recruiting	December 2017	Taiwan ... more >> Cvie Therapeutics Limited Recruiting Taipei, Taiwan, 100 Contact: Abby Chang, PhD    +886 2758 6003 ext 108    abbychang@cvie.com Collapse <<
  NCT01320397	Essential Hypertension	Phase 2	Unknown	December 2012	Ireland ... more >> Portiuncula Hospital Ballinasloe, Galway, Ireland James Connolly memorial Hospital Dublin, Ireland, 15 Clinical research centre, Beaumont Hospital Dublin, Ireland, 9 Italy Unità Operativa di Nefrologia e Dialisi, Ospedale "S. Maria della Scaletta" Imola, Bologna, Italy, 40026 Ospedale "Santa Maria" Borgo Val di Taro, Parma, Italy, 43023 Divisione di Cardiologia e UTIC Ospedale "Marianna Giannuzzi" Manduria, Taranto, Italy, 74024 Reparto di Emodialisi, Ospedale dell'Angelo Mestre, Venezia, Italy, 30174 U.O. di Nefrologia e Dialisi, Ospedale San Donato Arezzo, Italy, 52100 U.O Nefrologia, Dialisi e Ipertensione, Policlinico S. Orsola-Malpighi Bologna, Italy, 40138 Cattedra di Medicina Interna, U.O. Malattie Cardiovascolari, Policlinico Universitario Campus Germaneto Catanzaro, Italy, 88100 Centro per l'Ipertensione, Ospedale F. Veneziale Isernia, Italy, 86170 U.O.C. di Medicina Interna Universitaria 1, Ospedale San Salvatore L'Aquila, Italy, 67100 U.O. Nefrologia e Dialisi, Spedali Riuniti Livorno, Italy, 57100 Divisione di Nefrologia, Dialisi e Ipertensione Ospedale San Raffaele Milano, Italy, 20132 U.O. Nefrologia e Dialisi, Università degli Studi di Milano Azienda Ospedaliera San Paolo Milano, Italy, 20142 Clinica Medica 3, Dipartimento di Scienze Mediche e Chirurgiche Padova, Italy, 35128 Reparto Emodialisi, Clinica "Domus Nova" Ravenna, Italy, 48100 Nefrologia e Dialisi, Ospedale Infermi Rimini, Italy, 47900 Centro per l'Ipertensione, A.S.L. n° 1 Sassari, Italy, 07100 U.O. Nefrologia e Dialisi Presidio Ospedaliero "Giuseppe Mazzini" Teramo, Italy, 64100 Centro Ipertensione Arteriosa, SCU Medicina Interna 4, A.O.U. San Giovanni Battista Torino, Italy, 10126 Poland Institute of Cardiology, Department of Coronary Disease, Jagiellonian University Krakow, Poland, 31-202 Institute of Cardiology, I Department of Cardiology and Hypertension, Jagiellonian University Krakow, Poland, 31-501 Internal Medicine and Gerontology, Jagiellonian University Medical College Krakow, Poland, 31-501 Institute of Cardiology, Department of Hypertension, University of Medical Sciences Poznan, Poland, 01-848 The Cardinal Stefan Wyszynski Institute of Cardiology - Arterial Hypertension Clinic Warsaw, Poland, 04-628 Collapse <<

• 参考文献

• [1] Ferrari P, Ferrandi M, et al. Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R529-35.

  [2] Ferrari P. Rostafuroxin: an ouabain-inhibitor counteracting specific forms of hypertension. Biochim Biophys Acta. 2010 Dec;1802(12):1254-8.

  [3] Ferrari P. Rostafuroxin: an ouabain-inhibitor counteracting specific forms of hypertension. Biochim Biophys Acta. 2010 Dec;1802(12):1254-8

  [4] Ferrari P, Ferrandi M, Valentini G, Bianchi G. Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R529-35

  [5] Schoner W, Scheiner-Bobis G. Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth. Am J Physiol Cell Physiol. 2007 Aug;293(2):C509-36

  [6] Lingemann M, McCarty T, Liu X, Buchholz UJ, Surman S, Martin SE, Collins PL, Munir S. 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

• 更多

• Collapse