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To demonstrate that the reversible covalent warheads increase the cellular residence time as expected, we carried out cell-based wash-out experiments using the physiologically relevant AP-1 promoter-based reporter assay as well as the more direct NanoBRET target engagement assay

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The cell surface annotation rate was calculated using a subset of proteins expected to be exposed on the cell surface, which are annotated in UniProt 55 , Human Protein Atlas 56 and Gene Ontology (GO) cellular component 57,58 terms including cell membrane, cell surface, secreted (secretory granule, synaptic vesicle), endosomes (early, late, recycling, membrane), lysosome, plasma membrane (basal, apical, lateral, external side, raft), extracellular regions (space, matrix, vesicle, exosome), immunological synapse, cilium, intercellular bridge, membrane raft, junctions (adherens, bicellular tight, anchoring, cellcell), presynaptic membrane, early endosome, basement membrane, exocyst, ruffle membrane and focal adhesion (Supplementary Table 4)

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