Modulators of Na/K-ATPase: a patent review

Bibliography

• Skou JC, Esmann M. The Na,K-ATPase. J Bioenerg Biomembr 1992;24:249-61
   PubMed Web of Science ®Google Scholar
• Glynn IM. All hands to the sodium pump. J Physiol 1993;462:1-30
   PubMed Web of Science ®Google Scholar
• Glynn IM. A hundred years of sodium pumping. Annu Rev Physiol 2002;64:1-18
   PubMed Web of Science ®Google Scholar
• Pick U, Karlish SJD. Indications for an oligomeric structure and for conformational changes in sarcoplasmic reticulum Ca2+-ATPase labeled selectively with fluorescein. BBA Protein Struct M 1980;626:255-61
   PubMed Web of Science ®Google Scholar
• Repke KR, Schon R. Role of protein conformation changes and transphosphorylations in the function of Na+/K+-transporting adenosine triphosphatase: an attempt at an integration into the Na+/K+ pump mechanism. Biol Rev Camb Philos Soc 1992;67:31-78
   PubMed Web of Science ®Google Scholar
• Post RL, Hegyvary C, Kume S. Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J Biol Chem 1972;247:6530-40
   PubMed Web of Science ®Google Scholar
• Jorgensen PL, Hakansson KO, Karlish SJD. Structure and mechanism of Na, K-ATPase: functional sites and their interactions. Annu Rev Physiol 2003;65:817-49
   PubMed Web of Science ®Google Scholar
• Horisberger JD. Recent insights into the structure and mechanism of the sodium pump. Physiology 2004;19:377-87
   PubMed Web of Science ®Google Scholar
• Kaplan JH. Biochemistry of Na,K-ATPase. Annu Rev Biochem 2002;71:511-35
   PubMed Web of Science ®Google Scholar
• Lingrel JB, Arguello JM, Van Huysse J, Cation and cardiac glycoside binding sites of the Na, K-ATPase. Ann NY Acad Sci 1997;834:194-206
   PubMed Web of Science ®Google Scholar
• Barry WH, Hasin Y, Smith TW. Sodium pump inhibition, enhanced calcium influx via sodium-calcium exchange, and positive inotropic response in cultured heart cells. Circ Res 1985;56:231-41
   PubMed Web of Science ®Google Scholar
• Barry WH, Bridge JH. Intracellular calcium homeostasis in cardiac myocytes. Circulation 1993;87:1806-15
   PubMed Web of Science ®Google Scholar
• Sitsapesan R, Williams AJ. Regulation of current flow through ryanodine receptors by luminal Ca2+. J Membr Biol 1997;159:179-85
   PubMed Web of Science ®Google Scholar
• Scoote M, Williams AJ. The cardiac ryanodine receptor (calcium release channel): emerging role in heart failure and arrhythmia pathogenesis. Cardiovasc Res 2002;56:359-72
   PubMed Web of Science ®Google Scholar
• Dickstein K, Cohen-Solal A, Filippatos G, ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur J Heart Fail 2008;10:933-89
   PubMed Web of Science ®Google Scholar
• Geering K. The functional role of beta subunits in oligomeric P-type ATPase. J Bioenerg Biomembr 2001;33:425-38
   PubMed Web of Science ®Google Scholar
• Hasler U, Crambert G, Horisberger JD, Structural and functional features of the transmembrane domain of the Na,K-ATPase beta subunit revealed by tryptophan scanning. J Biol Chem 2001;276:16356-64
   PubMed Web of Science ®Google Scholar
• Pierre SV, Xie Z. The Na,K-ATPase receptor complex: its organization and membership. Cell Biochem Biophys 2006;46:303-15
   PubMed Web of Science ®Google Scholar
• Morth JP, Pedersen BP, Toustrup-Jensen MS. Crystal structure of the sodium-potassium pump. Nature 2007;450:1043-50
   PubMed Web of Science ®Google Scholar
• Shinoda T, Ogawa H, Cornelius F, Crystal structure of the sodium-potassium pump at 2.4A resolution. Nature 2009;459:446-51
   PubMed Web of Science ®Google Scholar
• Ogawa H, Shinoda T, Cornelius F, Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain. Proc Natl Acad Sci USA 2009;106:13742-7
   PubMed Web of Science ®Google Scholar
• Yatime L, Laursen M, Morth JP, Structural insights into the high affinity binding of cardiotonic steroids to the Na,K-ATPase. J Struct Biol 2011;174:296-306
   PubMed Web of Science ®Google Scholar
• Bublitz M, Poulsen H, Morth JP, In and out of the cation pumps: P-type ATPase structure revisited. Curr Opin Struct Biol 2010;20:431-9
   PubMed Web of Science ®Google Scholar
• Morth JP, Pedersen BP, Buch-Pedersen MJ, A structural overview of the plasma membrane Na+, K+-ATPase and H+-ATPase ion pumps. Nat Rev Mol Cell Biol 2011;12:60-70
   PubMed Web of Science ®Google Scholar
• Blanco G. Na,K-ATPase subunit heterogeneity as a mechanism for tissue-specific ion regulation. Semin Neurol 2005;25:292-303
   Google Scholar
• Shamraj OI, Lingrel JB. A putative fourth Na+, K+-ATPase a-subunit gene is expressed in testis. Proc Natl Acad Sci USA 1994;91:12952-6
   PubMed Web of Science ®Google Scholar
• Keryanov S, Gardner KL. Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4. Gene 2002;292:151-66
   PubMed Web of Science ®Google Scholar
• James PF, Grupp IL, Grupp G, Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart. Mol Cell 1999;3:555-63
   PubMed Web of Science ®Google Scholar
• Katz A, Lifshitz Y, Bab-Dinitz E, Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase. J Biol Chem 2010;285:19582-92
   PubMed Web of Science ®Google Scholar
• Mathieu V, Pirker C, De Lassalle EM, The sodium pump alpha1 subunit: a disease progression-related target for metastatic melanoma treatment. J Cell Mol Med 2009;13:3960-72
   PubMed Web of Science ®Google Scholar
• Xu ZW, Wang FM, Gao MJ, Targeting the Na/K-ATPase alpha1 subunit of hepatoma HepG2 cell line to induce apoptosis and cell cycle arresting. Biol Pharm Bull 2010;33:743-51
   PubMed Web of Science ®Google Scholar
• Mijatovic T, Roland I, Van Quaquebeke E, The alpha1 subunit of the sodium pump could represent a novel target to combat non-small cell lung cancers. J Pathol 2007;212:170-9
   PubMed Web of Science ®Google Scholar
• Lefranc F, Kiss R. The sodium pump alpha1 subunit as a potential target to combat apoptosis-resistant glioblastomas. Neoplasia 2008;10:198-206
   PubMed Web of Science ®Google Scholar
• Seligson DB, Rajasekaran SA, Yu H, Na,K-adenosine triphosphatase alpha1-subunit predicts survival of renal clear cell carcinoma. J Urol 2008;179:338-45
   PubMed Web of Science ®Google Scholar
• Shibuya K, Fukuoka J, Fujii T, Increase in ouabain-sensitive K-ATPase activity in hepatocellular carcinoma by overexpression of Na,K-ATPase alpha3-isoform. Eur J Pharmacol 2010;638:42-6
   PubMed Web of Science ®Google Scholar
• Yang P, Menter DG, Cartwright C, Oleandrin-mediated inhibition of human tumor cell proliferation: importance of Na,K-ATPase alpha subunit as drug targets. Mol Cancer Ther 2009;8:2319-28
   PubMed Web of Science ®Google Scholar
• Sakai H, Suzuki T, Mizuki M, Up-regulation of Na,K-ATPase alpha3-isoform and down-regulation of the a1-isoform in human colorectal cancer. FEBS Lett 2004;563:151-4
   PubMed Web of Science ®Google Scholar
• Mijatovic T, Van Quaquebeke E, Delest B, Cardiotonic steroids on the road to anti-cancer therapy. Biochim Biophys Acta 2007;1776:32-57
   PubMed Web of Science ®Google Scholar
• Mijatovic T, Ingrassia L, Facchini V, Na/K-ATPase alpha subunits as new targets in anticancer therapy. Expert Opin Ther Targets 2008;12:1403-17
   PubMed Web of Science ®Google Scholar
• Unibioscreen SA. Targeting alpha-1 or alpha-3 subunit of Na+,K+-ATPase in the treatment of proliferative diseases. 2008;WO2008055530
   Google Scholar
• Mijatovic T, Dufrasne F, Kiss R. Cardiotonic steroid-mediated targeting of the Na+/K+-ATPase to combat chemoresistant cancers. Curr Med Chem 2012;19:627-46
   PubMed Web of Science ®Google Scholar
• Liang M, Tian J, Liu L. Identification of a pool of non-pumping Na/K-ATPase. J Biol Chem 2007;282:10585-93
   PubMed Web of Science ®Google Scholar
• Haas M, Askari A, Xie Z. Involvement of src and epidermal growth factor receptor in the signal-transducing function of Na+/K+-ATPase. J Biol Chem 2000;275:27832-7
   PubMed Web of Science ®Google Scholar
• Wang H, Haas M, Liang M, Ouabain assembles signaling cascades through the caveolar Na+/K+-ATPase. J Biol Chem 2004;279:17205-59
   PubMed Web of Science ®Google Scholar
• Yuan Z, Cai T, Tian J, Na/K-ATPase tethers phospholipase C and IP3 receptor into a calcium-regulatory complex. Mol Biol Cell 2005;16:4034-45
   PubMed Web of Science ®Google Scholar
• Li Z, Xie Z. The Na/K-ATPase/Src complex and cardiotonic steroid-activated protein kinase cascades. Eur J Physiol 2009;457:635-44
   PubMed Web of Science ®Google Scholar
• Liu L, Ivanov AV, Gable ME, Comparative properties of caveolar and noncaveolar preparations of kidney Na+/K+-ATPase. Biochemistry 2011;50:8664-73
   PubMed Web of Science ®Google Scholar
• Weigand KM, Swarts HGP, Fedosova NU, Na,K-ATPase activity modulates Src activation: a role for ATP/ADP ratio. Biochim Biophys Acta 2012;1818:1269-73
   PubMed Web of Science ®Google Scholar
• Prassas I, Diamandis EP. Novel therapeutic applications of cardiac glycosides. Nat Rev Drug Discov 2008;7:926-35
   PubMed Web of Science ®Google Scholar
• Sales E, Meller-Uri F, Nebauer SG, Wild crop relatives: genomic and breeding resources, plantation and ornamental crops, Chapter 5. Digitalis. Springer-Verlag Berlin, Heidelberg;2011
   Google Scholar
• Albrecht HP, Geiss KH. Cardiac glycosides and synthetic cardiotonic drugs. Ullmann's encyclopedia of industrial chemistry. Wiley-VCH; 2000
   Google Scholar
• Karpova LV, Akkuratov EE, Brodskaya OM, The Na+ pump and intracellular signaling mechanisms. Biophysics 2010;55:1022-9
   Google Scholar
• Horowitz B, Eakle KA, Scheiner-Bobis G, Synthesis and assembly of functional mammalian Na,K-ATPase in yeast. J Biol Chem 1990;265:4189-92
   PubMed Web of Science ®Google Scholar
• Jochen ME, Padmaja J, Curtis TB, Ouabain and substrate affinities of human Na+-K+-ATPase alpha1beta1, alpha2beta1, and alpha3beta1 when expressed separately in yeast cells. Am J Physiol Cell Physiol 2001;281:C1355-64
   Google Scholar
• Strugatsky D, Gottschalk KE, Goldshleger R, Expression of Na+, K+-ATPase in Pichia pastoris. J Biol Chem 2003;278:46064-73
   PubMedGoogle Scholar
• Crambert G, Hasler U, Beggah AT, Transport and pharmacological properties of nine different human Na,K-ATPase isozymes. J Biol Chem 2000;275:1976-86
   PubMed Web of Science ®Google Scholar
• Blanco G, Xie Z, Mercer RW. Functional expression of the a2 and a3 isoforms of the Na,K-ATPase in baculovirus-infected insect cells. Proc Natl Acad Sci USA 1993;90:1824-8
   PubMed Web of Science ®Google Scholar
• Blanco G. The Na/K-ATPase and its isozymes: what we have learned using the baculovirus expression system. Front Biosci 2005;10:2397-411
   PubMed Web of Science ®Google Scholar
• Nishio M, Ruch SR, Wasserstrom JA. Positive inotropic effects of ouabain in isolated cat ventricular myocytes in sodium-free conditions. Am J Physiol Heart Circ Physiol 2002;283:2045-53
   Web of Science ®Google Scholar
• Geibel S, Kaplan JH, Bamberg E, Conformational dynamics of the Na+/K+-ATPase probed by voltage clamp fluorometry. Proc Natl Acad Sci USA 2003;100:964-9
   PubMed Web of Science ®Google Scholar
• Ahmed K, Rohrer DC, Fullerton DS, Interaction of (Na+,K+)-ATPases and digitalis genins, a general model for inhibitory activity. J Biol Chem 1983;258:8092-7
   PubMed Web of Science ®Google Scholar
• Gill S, Gill R, Wicks D, Development of an HTS assay for Na+, K+-ATPase using nonradioactive rubidium ion uptake. Assay Drug Dev Technol 2004;2:535-42
   PubMed Web of Science ®Google Scholar
• Kapakos JG, Steinberg M. Ligand binding to (Na,K)-ATPase labeled with 5-iodoacetamidofluorescein. J Biol Chem 1986;261:2084-9
   PubMed Web of Science ®Google Scholar
• Moczydlowski EG, Fortes PAG. Kinetics of cardiac glycoside binding to sodium, potassium adenosine triphosphatase studied with a fluorescent derivative of ouabain. Biochemistry 1980;19:969-77
   PubMed Web of Science ®Google Scholar
• Paula S, Tabet MR, Ball WJ Jr. Interactions between cardiac glycosides and sodium/potassium-ATPase: three-dimensional structural-activity relationship models for ligand binding to the E2-Pi form of the enzyme versus activity inhibition. Biochemistry 2005;44:498-510
   PubMed Web of Science ®Google Scholar
• Uhlen P. Visualization of Na,K-ATPase interacting proteins using FRET technique. Ann NY Acad Sci 2003;986:514-18
   PubMed Web of Science ®Google Scholar
• Kometiani P, Li J, Gnudi L, Multiple signal transduction pathways link Na+/K+-ATPase to growth-related genes in cardiac myocytes. J Biol Chem 1998;273:15249-56
   PubMed Web of Science ®Google Scholar
• Mohammadi K, Kometiani P, Xie Z, Role of protein kinase C in the signal pathways that link Na+/K+-ATPase to Erk1/2. J Biol Chem 2001;276:42050-6
   PubMed Web of Science ®Google Scholar
• Haas M, Wang H, Tian J, Src-mediated inter-receptor cross-talk between the Na+/K+-ATPase and the epidermal growth factor receptor relays the signal from ouabain to mitogen-activated protein kinases. J Biol Chem 2002;277:18694-702
   PubMed Web of Science ®Google Scholar
• Mobasheri A, Avila J, Cozar-Castellano I, Na+,K+-ATPase isozyme diversity; comparative biochemistry and physiological implications of novel functional interactions. Biosci Rep 2000;20:51-91
   PubMed Web of Science ®Google Scholar
• Huang YT, Chueh SC, Teng CM, Investigation of ouabain-induced anticancer effect in human androgen-independent prostate cancer PC-3 cells. Biochem Pharmacol 2004;67:727-33
   PubMed Web of Science ®Google Scholar
• Kometiani P, Liu L, Askari A. Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells. Mol Pharmacol 2005;67:929-36
   PubMed Web of Science ®Google Scholar
• Tian J, Li X, Liang M, Changes in sodium pump expression dictate the effects of ouabain on cell growth. J Biol Chem 2009;284:14921-9
   PubMed Web of Science ®Google Scholar
• McConkey DJ, Orrenius S. The role of calcium in the regulation of apoptosis. J Leuk Biol 1996;59:775-83
   PubMed Web of Science ®Google Scholar
• Ferrandi M, Manunta P, Balzan S, Ouabain-like factor quantification in mammalian tissues and plasma. Hypertension 1997;30:886-96
   PubMed Web of Science ®Google Scholar
• 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;293:509-36
   PubMed Web of Science ®Google Scholar
• Ferrari P, Ferrandi M, Valentini G, Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+-ATPase alterations in ouabain and adducing-dependent hypertension. Am J Physiol Regul Integr Comp Physiol 2006;290:R529-35
   Web of Science ®Google Scholar
• Antihypertensive effect of rostafuroxin compared with losartan in hypertensive patients bearing specified gene mutations. ClinicalTrials.gov. 2011 Available from: http://clinicaltrials.gov/ct2/show/NCT01320397 [Last accessed 12 February 2012]
   Google Scholar
• Staessen JA, Thijs L, Stolarz-Skrzypek K, Main results of the ouabain and adducin for specific intervention on sodium in hypertension trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin. Trials 2011;12:1-14
   PubMed Web of Science ®Google Scholar
• Jortani SA, Helm RA, Valdes R Jr. Inhibition of Na,K-ATPase by oleandrin and oleandrigenin, and their detection by digoxin immunoassays. Clin Chem 1996;42:1654-8
   PubMed Web of Science ®Google Scholar
• Manna SK, Sah NK, Newman RA, Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Cancer Res 2000;60:3838-47
   PubMed Web of Science ®Google Scholar
• McConkey DJ, Lin Y, Nutt LK, Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. Cancer Res 2000;60:3807-12
   PubMed Web of Science ®Google Scholar
• Newman RA, Yang P, Hittelman WN, Oleandrin-mediated oxidative stress in human melanoma cells. J Exp Ther Oncol 2006;5:167-81
   PubMedGoogle Scholar
• Newman RA, Kondo Y, Yokoyama T, Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a lipid-soluble cardiac glycoside. Integr Cancer Ther 2007;6:354-64
   PubMed Web of Science ®Google Scholar
• Yang P, Menter DG, Cartwright C, Oleandrin-mediated inhibition of human tumor cell proliferation: importance of Na,K-ATPase a subunits as drug targets. Mol Cancer Ther 2009;8:2319-28
   PubMed Web of Science ®Google Scholar
• Ozelle Pharmaceuticals, Inc. Extracts of nerium species, pharmaceutical composition thereof and methods for preparation thereof. 2003;US6565897B2
   Google Scholar
• Wang X, Plomley JB, Newman RA, LC/MS/MS analyses of an oleander extract for cancer treatment. Anal Chem 2000;72:3547-52
   PubMed Web of Science ®Google Scholar
• Pathak S, Multani AS, Narayan S, Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells. Anti Cancer Drug 2000;11:455-63
   PubMed Web of Science ®Google Scholar
• Mekhail T, Kaur H, Ganapathi R, Phase 1 trial of Anvirzel in patients with refractory solid tumors. Invest New Drugs 2006;24:423-7
   PubMed Web of Science ®Google Scholar
• Phoenix Biotechnology, Inc. Supercritical carbon dioxide extract of pharmacologically active components from Nerium oleander. 2008;US7402325B2
   Google Scholar
• Trial of PBI-05204 in advanced cancer patients. ClinicalTrials.gov. 2010 Available from: http://clinicaltrials.gov/ct2/show/NCT00554268 [Last accessed 12 February 2012]
   Google Scholar
• Gheorghiade M, Van Velhuisen DJ, Colucci WS. Contemporary use of digoxin in the management of cardiovascular disorders. Circulation 2006;113:2556-64
   PubMed Web of Science ®Google Scholar
• Ehle M, Patel C, Giugliano RP. Digoxin: clinical highlights. A review of digoxin and its use in contemporary medicine. Crit Pathw Cardiol 2011;10:93-8
   PubMedGoogle Scholar
• Winnicka K, Bielawski K, Bielawska A, Apoptosis-mediated cytotoxicity of ouabain, digoxin and proscillaridin A in the estrogen independent MDA-MB-231 breast cancer cells. Arch Pharm Res 2007;30:1216-24
   PubMed Web of Science ®Google Scholar
• Zhang H, Qian DZ, Tan YS, Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci USA 2008;105:19579-86
   PubMed Web of Science ®Google Scholar
• Yoshida T, Zhang H, Iwase T, Digoxin inhibits retinal ischemia-induced HIF-1alpha expression and ocular neovascularization. FASEB J 2010;24:1759-67
   PubMed Web of Science ®Google Scholar
• Gayed BA, O’Malley KJ, Pilch J, Digoxin inhibits blood vessel density and HIF-1alpha expression in castration-resistant C4-2 xenograft prostate tumors. Clin Transl Sci 2012;5:39-42
   PubMed Web of Science ®Google Scholar
• Svensson A, Azarbayjani F, Backman U, Digoxin inhibits neuroblastoma tumor growth in mice. Anticancer Res 2005;25:207-12
   PubMed Web of Science ®Google Scholar
• Belz GG, Breithaupt-Grogler K, Osowski U. Treatment of congestive heart failure – current status of use of digitoxin. Eur J Clin Invest 2001;31:10-17
   PubMed Web of Science ®Google Scholar
• Haux J. Digitoxin is a potential anticancer agent for several types of cancer. Med Hypotheses 1999;53:543-8
   PubMed Web of Science ®Google Scholar
• Haux J, Lam M, Marthinsen ABL, Digitoxin, in non toxic concentrations, induces apoptotic cell death in Jurket T cells in vitro. Z Onkol 1999;31:14-20
   Google Scholar
• Haux J, Solheim O, Isaksen T, Digitoxin, in non-toxic concentration, inhibits proliferation and induces cell death in prostate cancer cell lines. Z Onkol 2000;32:11-16
   Google Scholar
• Johansson S, Lindholm P, Gullbo J, Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells. Anti Cancer Drug 2001;12:475-83
   PubMed Web of Science ®Google Scholar
• Lopez-Lazaro M, Pastor N, Azrak SS, Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients. J Nat Prod 2005;68:1642-5
   PubMed Web of Science ®Google Scholar
• Lopez-Lazaro M. Digitoxin as an anticancer agent with selectivity for cancer cells: possible mechanisms involved. Expert Opin Ther Targets 2007;11:1043-53
   PubMed Web of Science ®Google Scholar
• Newman RA, Yang P, Pawlus AD, Cardiac glycosides as novel cancer therapeutic agents. Mol Interv 2008;8:36-49
   PubMed Web of Science ®Google Scholar
• Ahmed K, Rohrer DC, Fullerton DS, Interaction of (Na+,K+)-ATPase and digitalis genins. J Biol Chem 1983;258:8092-7
   PubMed Web of Science ®Google Scholar
• Yoda A. Structure-activity relationships of cardiotonic steroids for the inhibition of sodium- and potassium-dependent adenosine triphosphatase. Mol Pharmacol 1973;9:51-60
   PubMed Web of Science ®Google Scholar
• Fullerton DS, Kihara M, Deffo T, Cardiac glycoside 1. A systematic study of digitoxigenin D-glycosides. J Med Chem 1984;27:256-61
   PubMed Web of Science ®Google Scholar
• Rathore H, From AHL, Ahmed K, Cardiac glycoside 7. Sugar stereochemistry and cardiac glycoside activity. J Med Chem 1986;29:1945-52
   PubMed Web of Science ®Google Scholar
• Brown L, Erdmann E, Thomas R. Digitalis structure-activity relationship analyses. Conclusion from indirect binding studies with cardiac (Na++K+)-ATPase. Biochem Pharmacol 1983;32:2767-74
   PubMed Web of Science ®Google Scholar
• Chiu FCK, Watson TR. Conformational factors in cardiac glycoside activity. J Med Chem 1985;28:509-15
   PubMed Web of Science ®Google Scholar
• Langenhan JM, Peters NR, Guzei IA, Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization. Proc Natl Acad Sci USA 2005;102:12305-10
   PubMed Web of Science ®Google Scholar
• Wisconsin Alumni Research Foundation. Neoglycorandomization and digitoxin analogs. 2010;US20100256078
   Google Scholar
• Langenhan JM, Engle JM, Slevin LK, Modifying the glycosidic linkage in digitoxin analogs provides selective cytotoxins. Bioorg Med Chem Lett 2008;18:670-3
   PubMed Web of Science ®Google Scholar
• Langenhan JM, Endo MM, Engle JM, Synthesis and biological evaluation of RON-neoglycosides as tumor cytotoxins. Carbohydr Res 2011;346:2663-76
   PubMed Web of Science ®Google Scholar
• Zhou M, O’Doherty GA. De novo asymmetric synthesis of digitoxin via a palladium catalyzed glycosylation reaction. Org Lett 2006;8:4339-42
   PubMed Web of Science ®Google Scholar
• Zhou M, O’Doherty GA. De novo approach to 2-deoxy-beta-glycosides: asymmetric syntheses of digoxose and digitoxin. J Org Chem 2007;72:2485-93
   PubMed Web of Science ®Google Scholar
• Guo H, O’Doherty GA. De novo asymmetric synthesis of the Anthrax tetrasaccharide via a palladium catalyzed glycosylation reaction. Angew Chem Int Ed 2007;46:5206-8
   PubMed Web of Science ®Google Scholar
• Shan M, O’Doherty GA. De novo asymmetric synthesis of SL0101 and its analogues via a palladium-catalyzed glycosylation. Org Lett 2006;8:5149-52
   PubMed Web of Science ®Google Scholar
• Iyer AKV, Zhou M, Azad N, A direct comparison of the anticancer activities of digitoxin MeON-neoglycosides and O-glycosides. ACS Med Chem Lett 2010;1:326-30
   PubMed Web of Science ®Google Scholar
• Wang HYL, Xin W, Zhou M, Stereochemical survey of digitoxin monosaccharides. ACS Med Chem Lett 2011;2:73-8
   PubMed Web of Science ®Google Scholar
• Wang HYL, Rojanasakul Y, O’Doherty GA. Synthesis and evaluation of the alpha-D/alpha-L-rhamnosyl and amicetosyl digitoxigenin oligomers as antitumor agents. ACS Med Chem Lett 2011;2:264-9
   PubMed Web of Science ®Google Scholar
• Wang HYL, Wu B, Zhang Q, C5’-alkyl substitution effects on digitoxigenin alpha-L-glycoside cancer cytotoxicity. ACS Med Chem Lett 2011;2:259-63
   PubMed Web of Science ®Google Scholar
• Elbaz HA, Stueckle TA, Wang HYL, Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells. Toxicol Appl Pharmacol 2012;258:51-60
   PubMed Web of Science ®Google Scholar
• Jensen M, Schmidt S, Fedosova NU, Synthesis and evaluation of cardiac glycoside mimics as potential anticancer drugs. Bioorg Med Chem 2011;19:2407-17
   PubMed Web of Science ®Google Scholar
• Harris JM, Martin NE, Modi M. Pegylation, a novel process for modifying pharmacokinetics. Clin Pharmacokinet 2001;40:539-51
   PubMed Web of Science ®Google Scholar
• Juncker T, Schumacher M, Dicato M, UNBS1450 from Calotropis procera as a regulator of signaling pathways involved in proliferation and cell death. Biochem Pharmacol 2009;78:1-10
   PubMed Web of Science ®Google Scholar
• Van Quaquebeke E, Simon G, Andre A, Identification of a novel cardenolide (2”-oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structure-activity relationship analyses. J Med Chem 2005;48:849-56
   PubMed Web of Science ®Google Scholar
• Mijatovic T, Op De Beeck A, Van Quaquebeke E. The cardenolide UNBS1450 is able to deactivate nuclear factor kappaB-mediated cytoprotective effects in human non-small cell lung cancer cells. Mol Cancer Ther 2006;5:391-9
   PubMed Web of Science ®Google Scholar
• Juncker T, Cerella C, Teiten MH, UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells. Biochem Pharmacol 2011;81:13-23
   PubMed Web of Science ®Google Scholar
• Mijatovic T, De Neve N, Gailly P, Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity. Mol Cancer Ther 2008;7:1285-96
   PubMed Web of Science ®Google Scholar
• Mijatovic T, Mathieu V, Gaussin JF, Cardenolide-induced lysosomal membrane permeabilization demonstrates therapeutic benefits in experimental human non-small cell lung cancers. Neoplasia 2006;8:402-12
   PubMed Web of Science ®Google Scholar
• Lefranc F, Mijatovic T, Kondo Y, Targeting the alpha1 subunit of the sodium pump to combat glioblastoma cells. Neurosurgery 2008;62:211-22
   PubMed Web of Science ®Google Scholar
• Steyn PS, Van Heerden FR. Bufadienolides of plant and animal origin. Nat Prod Rep 1998;15:397-413
   PubMed Web of Science ®Google Scholar
• Nesher M, Shpolansky U, Rosen H, The digitalis-like steroid hormones: new mechanisms of action and biological significance. Life Sci 2007;80:2093-107
   PubMed Web of Science ®Google Scholar
• Nogawa T, Kamano Y, Yamashita A, Isolation and structure of five new cancer cell growth inhibitory bufadienolides from the Chinese traditional drug Ch’an Su. J Nat Prod 2001;64:1158-2
   Web of Science ®Google Scholar
• Kamano Y, Nogawa T, Yamashita A, Isolation and structure of a 20,21-epoxybufenolide series from “Ch’an Su”. J Nat Prod 2002;65:1001-5
   PubMed Web of Science ®Google Scholar
• Qiao L, Huang YF, Cao JQ, One new bufadienolides from Chinese drug “Chan’Su”. J Asian Nat Prod Res 2008;10:224-7
   Web of Science ®Google Scholar
• Tian HY, Wang L, Zang XQ, New bufadienolides and C23 steroids from the venom of Bufo bufo gargarizans. Steroids 2010;75:884-90
   PubMed Web of Science ®Google Scholar
• Qi F, Li A, Zhao L, Cinobufacini, an aqueous extract from Bufo bufo gargarizans Cantor, induces apoptosis through a mitochondria-mediated pathway in human hepatocellular carcinoma cells. J Ethnopharmacol 2010;128:654-61
   PubMed Web of Science ®Google Scholar
• Wang DL, Qi FH, Xu HL, Apoptosis-inducing activity of compounds screened and characterized from cinobufacini by bioassay-guided isolation. Mol Med Rep 2010;3:717-22
   PubMed Web of Science ®Google Scholar
• Xie CM, Chan WY, Yu S, Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radical Biol Med 2011;51:1365-75
   PubMed Web of Science ®Google Scholar
• Qi F, Li A, Inagaki Y, Induction of apoptosis by cinobufacini preparation through mitochondria- and Fas- mediated caspase-dependent pathways in human hepatocellular carcinoma cells. Food Chem Toxicol 2012;50:295-302
   PubMed Web of Science ®Google Scholar
• Gao H, Popescu R, Kopp B, Bufadienolides and their antitumor activity. Nat Prod Rep 2011;28:953-69
   PubMed Web of Science ®Google Scholar
• Meng Z, Yang P, Shen Y, Pilot study of Huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer. Cancer 2009;115:5309-18
   PubMed Web of Science ®Google Scholar
• Huachansu & Gemcitabine in pancreatic cancer. ClinicalTrials.gov. 2011 Available from: http://clinicaltrials.gov/ct2/show/NCT00837239 [Last accessed 20 February 2012]
   Google Scholar
• Kawazoe N, Aiuchi T, Masuda Y, Induction of apoptosis by bufalin in human tumor cells is associated with a change of intracellular concentration of Na+ ions. J Biochem 1999;126:278-86
   PubMed Web of Science ®Google Scholar
• Kamano Y, Yamashita A, Nogawa T, QSAR evaluation of the Ch’an Su and related bufadienolides against the colchicine-resistant primary liver carcinoma cell line PLC/PRF/5. J Med Chem 2002;45:5440-7
   PubMed Web of Science ®Google Scholar
• Ye M, Qu G, Guo H, Novel cytotoxic bufadienolides derived from bufalin by microbial hydroxylation and their structure-activity relationships. J Steroid Biochem 2004;91:87-98
   Google Scholar
• De Munari S, Cerri A, Gobbini M, Structure-based design and synthesis of novel potent Na,K-ATPase inhibitors derived from a 5alpha,14alpha-Androstane scaffold as positive inotropic compounds. J Med Chem 2003;46:3644-54
   PubMed Web of Science ®Google Scholar
• Gobbini M, Barassi P, Cerri A, 17alpha-O-(aminoalkyl)oxime derivatives of 3beta,14beta-dihydroxy-5beta-androstane and 3beta-hydroxy-14-oxoseco-D-5beta-androstane as inhibitors of Na+,K+-ATPase at the digitalis receptor. J Med Chem 2001;44:3821-30
   PubMed Web of Science ®Google Scholar
• Micheletti R, Mattera GG, Rocchetti M, Pharmacological profile of the novel inotropic agent (E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744). J Pharmacol Exp Ther 2002;303:592-600
   PubMed Web of Science ®Google Scholar
• Sitsapesan R, Williams AJ. Regulation of current flow through ryanodine receptors by luminal Ca2+. J Membr Biol 1997;159:179-85
   PubMed Web of Science ®Google Scholar
• Rocchetti M, Besana A, Mostacciuolo G, Modulation of sarcoplasmic reticulum function by Na+/K+ pump inhibitors with different toxicity: digoxin and PST2744 [(E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride]. J Pharmacol Exp Ther 2005;313:207-15
   PubMed Web of Science ®Google Scholar
• Alemanni M, Rocchetti M, Re D, Role and mechanism of subcellular Ca2+ distribution in the action of two inotropic agents with different toxicity. J Mol Cell Cardiol 2011;50:910-18
   PubMed Web of Science ®Google Scholar
• Shah SJ, Blair JE, Filippatos GS, Effects of istaroxime on diastolic stiffness in acute heart failure syndromes: results from the hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure (HORIZON-HF) trial. Am Heart J 2009;157:1035-41
   PubMed Web of Science ®Google Scholar
• University of medicine and dentistry of New Jersey. Novel pharmacophore for the discovery and testing of Na, K-ATPase inhibitor compositions and methods for their use in treating cardiovascular diseases and conditions. 2004;WO2004043384A2
   Google Scholar
• Zhang Z, Li Z, Tian J, Identification of hydroxyxanthones as Na/K-ATPase ligands. Mol Pharmacol 2010;77:961-7
   PubMed Web of Science ®Google Scholar
• The university of Toledo, Chinese academy of medical sciences. Na/K-ATPase ligands, ouabain antagonists, assays and uses thereof. 2011;WO2011034772
   Google Scholar
• Jang KH, Lee BH, Choi BW, Chromenes from the brown alga sargassum siliquastrum. J Nat Prod 2005;68:716-23
   PubMed Web of Science ®Google Scholar
• Campbell SE, Rudder B, Phillips RB, gamma-Tocotrienol induces growth arrest through a novel pathway with TGFb2 in prostate cancer. Free Radical Bio Med 2011;50:1344-54
   PubMed Web of Science ®Google Scholar
• Parker RA, Pearce BC, Clark RW, Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J Biol Chem 1993;268:11230-8
   PubMed Web of Science ®Google Scholar
• Chung SC, Jang KH, Park J, Sargachromanols as inhibitors of Na+/K+ ATPase and isocitrate lyase. Bioorg Med Chem Lett 2011;21:1958-61
   PubMed Web of Science ®Google Scholar
• Stonik VA, Makarieva TN, Dmitrenok AS. Sarcochromenol sulfates A-C and sarcohydroquinone sulfates A-C, new natural products from the sponge sarcotragus spinulosus. J Nat Prod 1992;55:1256-60
   PubMed Web of Science ®Google Scholar
• Stonik VA, Makarieva TN, Dmitrenok AS. Sarcochromenol sulfates A-C and sarcohydroquinone sulfates A-C, new natural products from the sponge sarcotragus spinulosus. J Nat Prod 1992;55:1256-60
   PubMed Web of Science ®Google Scholar
• Wagner H, Fessler B. In vitro 5-lipoxygenase inhibition by Eclipta alba extracts and the coumestan derivative wedelolactone. Planta Medica 1986;52:L374-7
   Google Scholar
• Kobori M, Yang Z, Gong D, Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibiting the IKK complex. Cell Death Differ 2004;11:123-30
   PubMed Web of Science ®Google Scholar
• Kumar R, Srinivasan S, Koduru S, Psoralidin, an herbal molecule, inhibits phosphatidylinositol 3-kinase-mediated Akt signaling in androgen-independent prostate cancer cells. Cancer Prev Res 2009;2:234-43
   PubMed Web of Science ®Google Scholar
• Wang W, Zhao YY, Liang H, Coumestans from Hedysarum multijugum. J Nat Prod 2006;69:876-80
   PubMed Web of Science ®Google Scholar
• Chen Y, Wei X, Xie H, Antioxidant 2-phenylbenofurans and a coumestan from Lespedeza virgata. J Nat Prod 2008;71:929-32
   PubMed Web of Science ®Google Scholar
• Da Silva AJ, Melo PA, Silva NM, Synthesis and preliminary pharmacological evaluation of coumestans with different patterns of oxygenation. Bioorg Med Chem Lett 2001;11:283-6
   PubMed Web of Science ®Google Scholar
• Pocas ES, Costa PR, Da Silva AJ, 2-Methoxy-3,8,9-trihydroxy coumestan: a new synthetic inhibitor of Na+,K+-ATPase with an original mechanism of action. Biochem Pharmacol 2003;66:2169-76
   PubMed Web of Science ®Google Scholar
• Pocas ES, Touza NA, Pimenta PH, Insights into the mechanism of Na+, K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan. Bioorg Med Chem 2008;16:8801-5
   PubMed Web of Science ®Google Scholar
• De Oliveira LFC, Edwards HGM, Velozo ES, Vibrational spectroscopic study of brazilin and brazilein, the main constituents of brazilwood from Brazil. Vib Spectrosc 2002;28:243-9
   Web of Science ®Google Scholar
• Baek NI, Jeon SG, Ahn EM, Anticonvulsant compounds from the wood of Caesalpinia sappan L. Arch Pharm Res 2000;23:344-8
   PubMed Web of Science ®Google Scholar
• Zhao YN, Pan Y, Tao JL, Study on cardioactive effects of Brazilein. Pharmacology 2006;76:76-83
   PubMed Web of Science ®Google Scholar
• Okamoto Y, Ojika M, Suzuki S, Iantherans A and B, unique dimeric polybrominated benzofurans as Na,K-ATPase inhibitors from a marine sponge, Ianthella sp. Bioorg Med Chem 2001;9:179-83
   PubMed Web of Science ®Google Scholar
• Okamoto Y, Nitanda N, Ojika M, Aplysiallene, a new bromoallene as an Na, K-ATPase inhibitor from the sea hare, Aplysia kurodai. Biosci Biotechnol Biochem 2001;65:474-6
   PubMed Web of Science ®Google Scholar
• Ho JH, Hong CY. Salvianolic acids: small compounds with multiple mechanisms for cardiovascular protection. J Biomed Sci 2011;18:30-4
   PubMed Web of Science ®Google Scholar
• Industry-Academic Cooperation Foundation. Prevention and treatment of atherosclerosis with lithospermate B. 2009;US20090227671
   Google Scholar
• Tzen JT, Jinn TR, Chen YC, Magnesium lithospermate B possesses inhibitory activity on Na+, K+-ATPase and neuroprotective effects against ischemic stroke. Acta Pharmacol Sin 2007;28:609-15
   PubMed Web of Science ®Google Scholar
• Qu J, Ren X, Hou RY, The protective effect of magnesium lithospermate B against glucose-induced intracellular oxidative damage. Biochem Biophys Res Commun 2011;411:32-9
   PubMed Web of Science ®Google Scholar
• Cardiovascular-protective effects of herbal medicine Danshen-Gegen. ClinicalTrials.gov. 2009 Available from: http://clinicaltrials.gov/ct2/show/NCT01033630 [Last accessed 20 February 2012]
   Google Scholar
• Chen YC, Jinn TR, Chung TY, Magnesium lithospermate B extracted from Salvia miltiorrhiza elevates intracellular Ca2+ level in SH-SY5Y cells. Acta Pharmacol Sin 2010;31:923-9
   PubMed Web of Science ®Google Scholar
• Chen RJ, Jinn TR, Chen YC, Active ingredients in Chinese medicines promoting blood circulation as Na+/K+-ATPase inhibitors. Acta Pharmacol Sin 2011;32:141-51
   PubMed Web of Science ®Google Scholar
• Jason Life Tech, Inc. Ltd. Method for inhibiting cellular Na+-K+ ATPase activity. 2007;US20070293462
   Google Scholar