Described herein are irreversible kinase inhibitor compounds having the structure:wherein:is an active site binding moiety selected fromY is a linker moiety and G is a Michael acceptor moiety； methods for synthesizing such irreversible inhibitors, and methods for using such irreversible inhibitors in the treatment of diseases. Further described herein are methods, assays and systems for determining an appropriate irreversible inhibitor of a protein, including a kinase.
