Figure 1. Ketone inhibitors were designed to mimic the tetrahedral intermediate of proposed mechanism B.

(A) Proposed Pin1 hydrogen-bond assisted twisted amide mechanism [25], (B) Pin1 Cys113 nucleophilic-addition mechanism tetrahedral intermediate proposed by Ranganathan et al [26]. (C) Electrophilic ketone inhibitor designed to mimic the proposed tetrahedral intermediate upon Cys113-S nucleophilic addition.