Interestingly, competition experiments with 2d and 2e showed relatively few significantly competed proteins, suggesting that many of the interactions involved sub-stoichiometric binding. This was true of CAII, where neither probes 2j or 2k showed competition with parents 2d or 2e, respectively. This is consistent with the slow rate of covalent modification of CAII by 2d and 2e in the biochemical kinetic analyses, which suggested that the protein would only be partially modified after a 1 h incubation. Together, these results indicate that while the aryl sulfonamide fragment hits did engage CAII in cells, it was with low stoichiometry and poor selectivity over many additional off-targets.