Na/K-ATPase Ligands, Ouabain Antagonists, Assays and Uses Thereof

Abstract

Na/K-ATPase/Src ligands, assays and uses thereof are disclosed.

1 . A Na/K-ATPase ligand, comprising at least one hydroxyl xanthone derivative having the structure: 
       
         
           
           
               
               
           
         
         wherein one or more of R 1 , R 3 , R 4 , R 5  and R 6  are selected from H, OH, OCH3, carboxylic acid ester, or analog thereof. 
       
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . A Na/K-ATPase ligand of  claim 1 , comprising MB5 wherein R 3 ═OH, R 4 ═OH and R 5 ═OH (3,4,5-trihydroxyxanthone. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . A method for inhibiting the ATPase activity without stimulating the receptor function of Na/K-ATPase in a cell in need thereof, comprising:
 administering an effective amount of at least one Na/K-ATPase ligand of  claim 1 .   
     
     
         11 . The method of  claim 10 , wherein the Na/K-ATPase ligand comprises MB5 (3, 4, 5-trihydroxyxanthone) and the effective amount ranges from about 40 pM to about 50 μM. 
     
     
         12 . (canceled) 
     
     
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         21 . (canceled) 
     
     
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         23 . (canceled) 
     
     
         24 . A composition for targeting the Na/K-ATPase/Src receptor complex and antagonizes cardiotonic steroid-induced protein kinase cascades in one or more cells in need thereof, comprising:
 at least one Na/K-ATPase ligand of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM.   
     
     
         25 . (canceled) 
     
     
         26 . A method for targeting the Na/K-ATPase-interacting pool of Src and acting as a potent cardiotonic steroid antagonist in one or more cells in need thereof, comprising:
 administering an effective amount of at least one Na/K-ATPase ligand comprised of a xanthone derivative of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM.   
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . A composition capable of selectively targeting the Na/K-ATPase-interacting pool of Src and of functioning as an effective ouabain antagonist in one or more cells in need thereof, comprising:
 at least one Na/K-ATPase ligand comprised of a xanthone derivative of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM.   
     
     
         30 . A therapeutic composition for cardiovascular diseases and cancer where the Na/K-ATPase/Src receptor is over-stimulated, comprising:
 at least one Na/K-ATPase ligand comprised of a xanthone derivative of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM.   
     
     
         31 . A method of inducing cell growth inhibition and/or cell death in a subject in need thereof, comprising:
 administering to the subject a therapeutically effective amount of at least one Na/K-ATPase ligand comprised of a xanthone derivative of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM.   
     
     
         32 . A composition for preventing CTS-provoked signaling pathway in a subject in need thereof, the composition comprising:
 at least one Na/K-ATPase ligand comprised of a xanthone derivative of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM.   
     
     
         33 . A method for substantially abolishing ouabain-provoked signaling transduction in the heart in a subject in need thereof, comprising:
 administering an effective amount of at least one Na/K-ATPase ligand comprised of a xanthone derivative of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM.   
     
     
         34 . (canceled) 
     
     
         35 . A pharmaceutical composition comprising at least one Na/K-ATPase ligand comprised of a xanthone derivative of  claim 4 , present in an amount ranging from about 40 pM to about 50 μM, and a physiologically acceptable carrier. 
     
     
         36 . The composition of  claim 35 , wherein the composition is adapted for use as a treatment for cardiac hypertrophy, tissue fibrosis and/or congestive heart failure. 
     
     
         37 .- 61 . (canceled)