The Meisenheimer Complex as a Paradigm in Drug Discovery: Reversible Covalent Inhibition through C67 of the ATP Binding Site of PLK1 (Cell Chemical Biology)

Pearson et al. describe the structure-guided discovery of benzothiazole N-oxide PLK1 inhibitors that bind covalently with C67 through Meisenheimer complexes. These represent prototypes to exploit this unique mechanism of inhibition in drug discovery to achieve high specificity and still bind reversibly.