In general, these chemoproteomic efforts are not targeted -instead, they yield large datasets on the ligandability of thousands of cysteine residues. These datasets can be leveraged for the development of covalent inhibitors, probes, and degraders for a variety of protein targets, particularly for non-active site cysteine residues. However, published proteome-wide ligandability screens have not yielded any substantial leads for PTP active site cysteine residues. Rather, these screens suggest that PTP catalytic cysteines are not very reactive relative to the entire proteome, despite their low pKa values, and they are apparently unliganded by most fragments used in existing screens. Consequently, it is difficult to extract information from these global ligandability screens on how different structures impact covalent inhibition of PTPs.