Inhibition of the SRC kinase family pathway as a method of treating HBV infection and hepatocellular carcinoma

Abstract

The present invention relates to therapeutic protocols and pharmaceutical compositions designed to target HBx mediated activation of Src kinase, members of the Src 5 tyrosine kinase family and components of the Src kinase family signal transduction pathways for the treatment of HBV infection and related disorders and diseases, such as HCC. The invention further relates to pharmaceutical compositions for the treatment of HBV infection targeted to HBx and its essential activities required to sustain HBV replication. The invention is based, in part, on the Applicants' discovery that activation of Src kinase signaling cascades play a fundamental role in mammalian hepadnavirus replication. Applicants have demonstrated that HBx mediates activation of the Src family of kinases and that this activation is a critical function provided by HBx for mammalian hepadnavirus replication.

1 .- 51 . (canceled)  
     
     
         52 . A pharmaceutical formulation for the treatment of HBV infection, comprising a compound that inhibits the activity of a Src kinase in an amount effective to inhibit HBV replication, and a pharmaceutically acceptable carrier.  
     
     
         53 . The pharmaceutical composition of claim  1 , wherein said peptide is a tyrosine kinase inhibitor or dominant-negative mutant of Fyn, Hck, Yes or another Src kinase member.  
     
     
         54 . The pharmaceutical composition of claim  1 , wherein said peptide tyrosine kinase inhibitor is Csk.  
     
     
         55 . The pharmaceutical composition of claim  1 , wherein said compound is a tyrphostin-derived tyrosine kinase inhibitor or a pharmaceutically acceptable salt thereof.  
     
     
         56 . The pharmaceutical composition of claim  1 , wherein said compound is a benzylidenemalonitrile derivative or a pharmaceutically acceptable salt thereof.  
     
     
         57 . The pharmaceutical composition of claim  1 , wherein said compound is pyrazolopyrimidine PP1 or a pharmaceutically acceptable salt thereof.  
     
     
         58 . The pharmaceutical composition of claim  1 , wherein said compound is angelmycin B or a pharmaceutically acceptable salt thereof.  
     
     
         59 . The pharmaceutical composition of claim  1 , wherein said compound is a phosphotyrosine containing ligand or a pharmaceutically acceptable salt thereof.