A key concern in fragment screening is deconvolution of specific versus non-specific interactions. In traditional fragment screening, the latter is usually associated with high lipophilicity or low solubility of the fragment. Electrophilic fragment screens can yield non-selective hits due to high reactivity of the electrophilic warhead, leading to labelling of surface-exposed cysteine residues. An analogous consideration for photoaffinity labelling is that the reactive intermediate formed upon irradiation should be appropriately short-lived to avoid diffusion-based crosslinking that is not driven by binding affinity. The majority of the PhABits did not crosslink to the proteins screened, indicating that the reactive intermediate was rapidly quenched. However, ten PhABits were found to crosslink to all proteins screened and 58 crosslinked to at least four proteins. These could represent privileged scaffolds that are accommodated by many protein pockets, or be due to non-specific crosslinking either through lipophilic interactions with the protein or formation of long-lived reactive species.