Lipoxin compounds and their use in treating cell proliferative disorders

Abstract

Compounds having the active site of natural lipoxins, but a longer tissue half-life are disclosed. In particular, 15-epi-lipoxins and their use in ameliorating undesired cell proliferation, which characterizes diseases such as cancer, are also disclosed.

1 . A lipoxin compound having an active region of a natural lipoxin, wherein the active region of the natural lipoxin is either C5-C15 of lipoxin A4, or C5-C14 of lipoxin B4 as shown below: 
       
         
           
           
               
               
           
         
       
     
     
         2 . A lipoxin compound according to  claim 1 , wherein the natural lipoxin is lipoxin A4, which is not converted to a 15-oxo or 13-14-dihydro metabolite when administered to a subject in vivo or when cultured with monocytes in vitro. 
     
     
         3 . A lipoxin compound according to  claim 2 , which binds to an LXA 4  specific receptor on differentiated HL-60 cells or leukocytes in a homologous displacement assay with a K d  comparable to or less than 0.6±0.3 nM. 
     
     
         4 . A lipoxin compound according to  claim 1 , wherein the natural lipoxin is lipoxin B4, which is not converted to a 5-oxo or 6-7-dihydro metabolite when administered to a subject in vivo or when cultured with monocytes in vitro. 
     
     
         5 . The lipoxin compound of  claim 1 , further including a metabolic transformation region resistant to in vivo metabolism as found in lipoxin A 4 . 
     
     
         6 . A pharmaceutical composition for inducing vasodilation to treat or prevent a vscocontractive response or conditions comprising a pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         7 . A pharmaceutical composition for treating restenosis in a subject in need thereof comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         8 . A pharmaceutical composition for treating vasoconstriction comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier.