Figure 1. Activities of 147 analogs toward ATF6 activation.
(A) Structure of 147 with its three components – the A-ring, B-ring, and linker – indicated. (B) Bar graph showing the relative activation of the ERSE.FLuc ATF6 transcriptional reporter in HEK293T cells treated with 147 (10 µM; 18 hr), the ER stressor thapsigargin (Tg; 0.5 µM; 18 hr), or the indicated analogs of 147 where the A-ring was varied (10 µM; 18 hr). Error bars show SEM for three technical replicates. (C) Bar graph as in (B) where HEK293T cells were treated with the indicated 147 analogs where the linker was varied (10 µM; 18 hr). Error bars show SEM for three technical replicates. (D) Bar graph as in (B) where HEK293T cells were treated with the indicated 147 analogs in which a bromine atom was placed in the ortho, para, and meta positions of the B-ring (10 µM; 18 hr). Error bars show SEM for three technical replicates. (E) Bar graph as in (B) where HEK293T cells were treated with the indicated 147 analogs with a variety of substituents incorporated onto the B-ring. Error bars show SEM for three technical replicates.
Figure 1—figure supplement 1. Synthetic schemes used to prepare analogs of 147.
