Optimization through commercially available analogues and synthesis. Commercially available analogues of the two compounds shown in Figure were also tested (Table ). Unfortunately, the lack of diversity of CSSS28078573 analogues did not allow an in-depth structure activity relationship. However, the drop in activity of compound CSSS26687349 with both ubiquitin and peptide as substrate suggested that ortho-substitution was not tolerated on the terminal phenyl ring. More diversity was found for the CSSS28008898 series but revealed that several modifications on the left-hand side of the molecule were tolerated, this group being predicted to be in the open P4+ pockets.