Compositions and methods of treating cardiac hypertrophy and heart failure

Abstract

A method of treating cardiac hypertrophy and/or heart failure in a subject includes administering to the subject a therapeutically effective amount of a REV-ERBα agonist.

What is claimed is: 
     
         1 . A method of treating cardiac hypertrophy in a subject in need thereof, the method comprising:
 administering to the subject a therapeutically effective amount of a REV-ERBα agonist.   
     
     
         2 . The method of  claim 1 , the REV-ERBα agonist selected from the group consisting of 1,1-Dimethylethyl N-[(4-chlorophenyl)methyl]-N-[(5-nitro-2-thienyl)methyl])glycinate (SR6452); N-Benzyl-N-(4-chlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine; N-Benzyl-N-(3,4-dichlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine; 2-((4-chlorobenzyl)((5-nitrothiophen-2-yl)methyl)amino)-N,N-dimethylacetamide, SR9009, SR9011 and pharmaceutically acceptable salts thereof. 
     
     
         3 . The method of  claim 2 , the REV-ERBα agonist selected from the group consisting of SR9009 and SR6452. 
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective amount is the amount required to inhibit cardiomyocyte hypertrophic growth in the subject. 
     
     
         5 . The method of  claim 1 , wherein the therapeutically effective amount is the amount required to reduce cardiac fibrosis and/or cardiac cell death in the subject. 
     
     
         6 . The method of  claim 1 , wherein the REV-ERBα agonist is administered to the subject by at least one of oral and/or parenteral delivery. 
     
     
         7 . A method of treating heart failure in a subject in need thereof, the method comprising:
 administering to the subject a therapeutically effective amount of a REV-ERBα agonist.   
     
     
         8 . The method of  claim 7 , the REV-ERBα agonist selected from the group consisting of 1,1-Dimethylethyl N-[(4-chlorophenyl)methyl]-N-[(5-nitro-2-thienyl)methyl])glycinate (SR6452); N-Benzyl-N-(4-chlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine; N-Benzyl-N-(3,4-dichlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine; 2-((4-chlorobenzyl)((5-nitrothiophen-2-yl)methyl)amino)-N,N-dimethylacetamide, SR9009, SR9011 and pharmaceutically acceptable salts thereof. 
     
     
         9 . The method of  claim 8 , the REV-ERBα agonist selected from the group consisting of SR9009 and SR6452. 
     
     
         10 . The method of  claim 7 , wherein the therapeutically effective amount is the amount required to inhibit cardiomyocyte hypertrophic growth in the subject. 
     
     
         11 . The method of  claim 7 , wherein the therapeutically effective amount is the amount required to reduce cardiac fibrosis and/or cardiac cell death in the subject. 
     
     
         12 . The method of  claim 7 , wherein the REV-ERBα agonist is administered to the subject by at least one of oral and/or parenteral delivery. 
     
     
         13 . A method of inhibiting cardiac fibrosis in a subject in need thereof, the method comprising:
 administering to the subject a therapeutically effective amount of a REV-ERBα agonist.   
     
     
         14 . The method of  claim 13 , the REV-ERBα agonist selected from the group consisting of 1,1-Dimethylethyl N-[(4-chlorophenyl)methyl]-N-[(5-nitro-2-thienyl)methyl])glycinate (SR6452); N-Benzyl-N-(4-chlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine; N-Benzyl-N-(3,4-dichlorobenzyl)-1-(5-nitrothiophen-2-yl)methanamine; 2-((4-chlorobenzyl)((5-nitrothiophen-2-yl)methyl)amino)-N,N-dimethylacetamide, SR9009, SR9011 and pharmaceutically acceptable salts thereof. 
     
     
         15 . The method of  claim 14 , the REV-ERBα agonist selected from the group consisting of SR9009 and SR6452. 
     
     
         16 . The method of  claim 13 , wherein the therapeutically effective amount is the amount required to inhibit cardiomyocyte hypertrophic growth in the subject. 
     
     
         17 . The method of  claim 13 , wherein the therapeutically effective amount is the amount required to reduce cardiac cell death in the subject. 
     
     
         18 . The method of  claim 13 , wherein the REV-ERBα agonist is administered to the subject by at least one of oral and/or parenteral delivery.