Next, the CatB and S inhibitory activities of the compounds were inspected. By trend, a less pronounced inhibition of CatB was observed in comparison to CatL (Table ). On the contrary, the compounds were highly potent inhibitors of CatS. This finding was expected because leucine is known as a preferred P2 amino acid in CatS substrates and the Leu-Phe dipeptide as an advantageous P2-P1 pattern in peptidomimetic CatS inhibitors. The majority of compounds did not show CatB inhibition, and 5b, 11b, 12a, and 14a exhibited Ki values in the range of 9 µM to 22 µM. These four compounds inhibited CatS with Ki values between 5 nM and 118 nM. Three compounds were potent CatB inhibitors, i.e., 9a, 9b, and 9c, with Ki values lower than 220 nM. Even these three peptide aldehydes had a clear preference for CatL over CatB, with Ki values being lower by one order of magnitude (Table ). However, 9a, 9b, and 9c were identified as sub-nanomolar or single-digit nanomolar CatS inhibitors (Table ).