Figure 5. A screen of carmaphycin B and 11 analogs identifies a compound that preferentially inhibits Sm20S with decreased cytotoxicity to HepG2 cells.

A. Structure of carmaphycin B and IC₅₀ values for this compound against each catalytic subunit of Sm20S, c20S and i20S B. Inhibition of Sm20S by 11 carmaphycin B analogs (red heatmap) that have lower HepG2 cytotoxicity than the parent molecule (toxicity data and numbering system taken from LaMonte et al⁴⁷). Activity of Sm20S was quantified in the presence of 10 nM inhibitor for β5 and β1 assays and 50 nM inhibitor for β2 assays. Mean % inhibition values relative to vehicle (DMSO) are shown . C. Structures of carmaphycin B analogs 1, 7 and 17. D. Mean IC₅₀ values for carmaphycin B analogs 1, 7 and 17 for each catalytic subunit of the Sm20S, c20S and i20S.