Upon docking to POP, the N-Cbz boronic ester derivative 10c was observed to fit very well into the active site of POP (Figure ), while docking to FAP gave unfavorable proposed binding modes, as the carboxybenzyl group is too large to fit into the active site (not shown). This compound is therefore expected to be selective for POP. After virtual optimization of the amide side chain, the acetyl group turned out to be an excellent compromise for the design of potent dual inhibitors, as key interactions were conserved. The N-acetyl group may act as a hydrogen bond donor in FAP (with Glu203 or 204) and as a hydrogen bond acceptor in POP (with Trp595). The docking-predicted binding mode of the N-acetyl analog in both POP and FAP is shown in Figure . Furthermore, in order to evaluate the impact of the covalent warhead, the non-covalent analog 10b was also prepared.