20-hete receptor (gpr75) antagonists and methods of use

Abstract

The present invention concerns compounds and their use to treat cardiovascular disease, renal disease, thrombic disease, stroke, metabolic syndrome, cell proliferation, and ischemic cardiovascular disorders. Compounds of the present invention display significant potency as antagonists of 20-hydroxyeicosatetraenoic acid (20-HETE), and function as anti-hypertensive, anti-inflammatory, or anti-growth agents.

1 - 33 . (canceled) 
     
     
         34 . A method of identifying a 20-HETE antagonist, comprising the steps of:
 a) providing a polypeptide comprising the amino acid sequence of SEQ ID NO: 2;   b) screening a library of candidate compounds for binding to said polypeptide; and   c) identifying a compound capable of binding to said polypeptide and acting as a 20-HETE antagonist.   
     
     
         35 . The method of  claim 34 , wherein said 20-HETE antagonist reduces 20-HETE-mediated association of said polypeptide with a protein selected from the group consisting of GIT1 and HIC-5. 
     
     
         36 . The method of  claim 34 , wherein said step (a) further comprises: providing a protein selected from the group consisting of GIT1 and HIC-5. 
     
     
         37 . The method of  claim 34 , wherein said screening comprises immunoprecipitation. 
     
     
         38 . The method of  claim 37 , wherein said screening further comprises immunoblotting. 
     
     
         39 . The method of  claim 34 , wherein said step (a) further comprises providing a cell comprising said polypeptide. 
     
     
         40 . The method of  claim 39 , wherein the cell is a human cell. 
     
     
         41 . The method of  claim 34 , wherein said step (a) further comprises providing a membrane fraction of a cell comprising said polypeptide. 
     
     
         42 . The method of  claim 41 , wherein said cell is a human cell. 
     
     
         43 . The method of  claim 34 , wherein said identifying comprises identifying a plurality of compounds capable of binding to said polypeptide and acting as 20-HETE antagonists.