Use of atr and chk1 inhibitor compounds

Abstract

The invention relates to kinase inhibitor compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating or preventing herpesvirus infection and/or herpesvirus-associated diseases and disorders.

1 . A method of treating or preventing a herpesvirus infection in a subject comprising administering to the subject identified as in need thereof a compound selected from Table 1 or salt, hydrate or solvate thereof. 
     
     
         2 . The method of  claim 1 , wherein the subject is administered an additional therapeutic agent. 
     
     
         3 . The method of  claim 2 , wherein the compound selected from Table 1 or salt, hydrate or solvate thereof and the additional therapeutic agent are administered simultaneously. 
     
     
         4 . The method of  claim 2 , wherein the compound selected from Table 1 or salt, hydrate or solvate thereof and the additional therapeutic agent are administered sequentially. 
     
     
         5 . The method of  claim 1 , wherein the herpesvirus is HSV-1 or HSV-2. 
     
     
         6 . The method of  claim 1 , wherein the compound selected from Table 1 or salt, hydrate or solvate thereof inhibits ATR-mediated DNA-damage-checkpoint pathway. 
     
     
         7 . The method of  claim 1 , wherein the compound selected from Table 1 or salt, hydrate or solvate thereof is an inhibitor of ATR. 
     
     
         8 . The method of  claim 7 , wherein the inhibitor of ATR is selected from the group consisting of VE-821, VE-822, AZD6738, AZ20, NVP-BEZ235, ETP-46464, NU6027, and Schisandrin B. 
     
     
         9 . The method of  claim 1 , wherein the compound selected from Table 1 or salt, hydrate or solvate thereof is an inhibitor of Chk1. 
     
     
         10 . The method of  claim 9 , wherein the inhibitor of Chk1 is selected from the group consisting of CHIR 124, PF-00477736, AZD7762, SCH900776/MK-8776, IC83/LY2603618, LY2606368, GDC-0425, XL844, SAR-020106, and CCT-244747. 
     
     
         11 . The method of  claim 1 , wherein the compound selected from Table 1 or salt, hydrate or solvate thereof does not inhibit ATM. 
     
     
         12 . The method of  claim 1 , wherein the herpesvirus is HSV-1, HSV-2, Varicella zoster virus, Epstein-Barr virus, human herpesvirus 6, human herpesvirus 7, Kaposi's sarcoma-associated herpesvirus, Pseudorabies virus, gaHV-2, BHV-1, or EHV-1. 
     
     
         13 - 15 . (canceled) 
     
     
         16 . A method for reducing HSV viral replication comprising contacting a cell with an ATR-mediated DNA-damage-checkpoint pathway inhibitor compound. 
     
     
         17 . A method of inhibiting HSV in a subject identified as-in need of such treatment, comprising administering a compound of Table 1 or salt, hydrate or solvate thereof. 
     
     
         18 - 20 . (canceled)