Interestingly, the ratios of cell-free to cellular potencies of the shared hits clustered with their reactivity (Fig. ). The SNAr-reactive species had near-identical cell-free and cellular potencies; heavy metals and nitrosylating agent Dephostatin had >10-fold potency loss in cells; and Michael system electrophiles up to ~100-fold potency loss. The on-target potency of irreversibly reactive compounds in cellular assays is strongly ruled by their biolocalisation and reaction rates with off-target species. We expect that our data comparison (Fig. ) reflects the degree of undesirable drug loss to offtargets according to compound class; and we propose that the superior cellular translation of the selenophilic tempered SNAr electrophiles suggests how drug development can pursue both effective and selective inhibitors of this key oxidoreductase.