Protein kinases play important roles in many physiological processes.The abnormal activation of kinases were hallmarks of many cancer-related diseases.So much efforts have been devoted to developing small-molecule inhibitors that regulate kinase activity and can be used as drugs for therapy.Due to high sequence and structural similarity in their catalytic domain,it still remains challenging to design potent and yet specific inhibitors with minimum off-target and cytotoxic effects for kinases.A large number of kinase inhibitors are reversible,which are ATP analogue and compete with ATP binding to inhibit kinases activity,The other categrory is irreversible kinase inhibitor which act by covalent modification of reactive amino acids,such as cysteine,in kinases to achieve inhibition.In this project,we aim to develope a quantitative chemoproteomic profiling technology to comprehensively indentify and quantify protein targets of irreversible kinase inhibitors in proteomes.