This talk will describe state-of-the-art chemical proteomic platforms that enable interrogation of cell state-dependent changes in the proteomes of immune cells and identification of new opportunities for the development of covalent small-molecule protein degraders. It will further introduce a chemical biology strategy that leverages stereoisomeric elaborated electrophiles in phenotypic screening that allowed for the discovery of a compound that stereoselectively blocks T cell activation and promotes the degradation of key immune kinase ITK in stimulated, but not resting T cells, thus reflecting a rare example of cell state-restricted pharmacology.