Fig. 3. State-of-the-art chemoproteomic approaches for reimaging druggable proteome and selectivity profiling of covalent fragments. (A) Activity-based protein profiling (IsoTOP-ABPP and TMT-ABPP) using isotope-labeled probes or isotopic TMT labeling agents for multiplex quantitative chemoproteomics.^39,54–57 (B) Covalent Inhibitor Target-site Identification (CITe-Id), another complementary chemoproteomic platform to understand the proteome-wide on/off-target effect in covalent fragment development program, in which desthiobiotinylated covalent inhibitor is used in lieu of non-selective iodoacetamide probe to directly monitor target engagement.⁵⁸ (C) Cysteine-Reactive Phosphate Tags (CPTs) developed recently can be applied as a chemoproteomic using phosphate-tagged iodoacetamide for global cysteine profiling with high coverage of the cysteine proteome.⁵⁹.