Methods for predicting kinase inhibitor resistance

Abstract

Provided are methods for the identification of mutant kinases that are resistant to inhibition by a kinase inhibitor. In some embodiments, the methods may be used to assess a test compound or kinase inhibitor for the risk of the development of resistance in vivo, e.g., during clinical administration to treat a disease such as a cancer.

1 - 47 . (canceled) 
     
     
         48 . An isolated mutant ABL kinase, wherein the mutant ABL kinase comprises a substitution mutation selected from the group consisting of Table 3; with amino acid position numbering being according to the Kabat system. 
     
     
         49 . The isolated mutant ABL kinase, wherein the substitution mutation is V488L. 
     
     
         50 . The isolated mutant ABL kinase, wherein the substitution mutation is F493L or D445G. 
     
     
         51 . A nucleic acid encoding the mutant ABL kinase of  claim 48 . 
     
     
         52 . The nucleic acid of  claim 51 , wherein the mutant ABL kinase comprises the substitution mutation V488L. 
     
     
         53 . A host cell that recombinantly expresses the isolated mutant ABL kinase of  claim 48 . 
     
     
         54 . The host cell of  claim 53 , wherein the mutant ABL kinase comprises the substitution mutation V488L. 
     
     
         55 . The host cell of  claim 53 , wherein the cell is a eukaryotic cell. 
     
     
         56 . The host cell of  claim 55 , wherein the eukaryotic cell is a yeast cell.