(A) Individual inhibition
plots of active compounds 1, 2, and 3 and inactive compounds 5, 6, and 7. 3 was
dosed at 1 μM, while 1, 2, and the
inactive analogues were dosed at 10 μM. The vertical and horizontal
threshold lines represent a log2 change of −1 and
a log10(P value) of −1.3 (two-sided
two-sample t-test, n = 3 independent
experiments per group), respectively. Green dots indicate proteins
that are probe targets, as defined in Table S9. (B) Venn diagram showing the overlap of >50% inhibited proteins
between 3 and inactive analogues 5–7. (C) Relative general protein levels in strains resistant
to 3 compared to WT. Each group was compared to WT using
a two-sided two-sample t-test, n = 3 independent experiments per group. Statistical significance:
***P < 0.001; **P < 0.01;
*P < 0.05; n.s. if P > 0.05.
(D) Relative protein levels enriched by 4 in strains
resistant to 3 (Figure 2B) compared to wild type. Each group was compared to
WT using a two-sided two-sample t-test, n = 3 independent experiments per group.