Kidney-targeted epoxyeicosatrienoic acid (eet) analogs

Abstract

Described here are EET analogs conjugated to folate receptor ligands such as folic acid or folic acid analogs recognized by and selectively bound by folate receptors and other folate binding proteins and the use of such conjugated EET analogs for targeted delivery of therapeutic agents to folate-receptor bearing cell populations. More particularly, provided herein are EET analogs conjugated to folate receptor ligands and uses of such conjugated EET analogs as kidney targeted therapeutics.

1 . A compound comprising an EET analog conjugated to folic acid or methotrexate, wherein the EET analog used to prepare the compound has a formula selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         2 . The compound of  claim 1 , wherein the EET analog is conjugated to folic acid. 
     
     
         3 . The compound of  claim 1 , wherein the EET analog is 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1 , wherein the EET analog is 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 1 , wherein the EET analog is 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1 , wherein the EET analog is 
       
         
           
           
               
               
           
         
       
     
     
         7 . A pharmaceutical composition comprising the compound according to  claim 1  and at least one component selected from the group consisting of a pharmaceutically acceptable carrier, excipient, or diluent. 
     
     
         8 . A method of treating kidney disease in a subject in need thereof, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of  claim 7  to the subject, whereby the kidney disease is treated. 
     
     
         9 . A method of reducing nephrotoxicity in a subject in need thereof, the method comprising administering a therapeutically effective amount of the pharmaceutical composition of  claim 7  to the subject, whereby the nephrotoxicity is reduced. 
     
     
         10 . The method of  claim 9 , wherein the nephrotoxicity is drug-induced. 
     
     
         11 . The method of  claim 9 , wherein the nephrotoxicity is cisplatin-induced. 
     
     
         12 . A pharmaceutical composition comprising the compound according to  claim 2  and at least one component selected from the group consisting of a pharmaceutically acceptable carrier, excipient, or diluent 
     
     
         13 . A method for delivering a therapeutic agent to a target cell population comprising a folate receptor, the method comprising providing the pharmaceutical composition of  claim 12  and contacting the target cell population with a therapeutically effective amount of the pharmaceutical composition to permit binding of the compound to the folate receptor.