(A) Chemical structure of KIRA8. (B) Ethidium bromide-stained agarose gel of XBP1 cDNA amplicons after induction by treating Mouse Lung Epithelial (MLE12) cells with Tunicamycin (Tun) 0.5 μg/ml and indicated concentrations of KIRA7 or KIRA8 for 8 hrs. The ratio of spliced over (spliced + unspliced) amplicons—1S/(1S+2U+3U)—is reported as % XBP1 splicing and reported under respective lanes. (C) Schematic of the KIRA8 reversal regimen. Mice were exposed to saline or bleomycin once, then treated with KIRA8 or vehicle beginning two weeks after bleomycin exposure and continuing daily for two additional weeks. (D) Western blot of terminal UPR transcription factors XBP1s, ATF4, and CHOP from mice treated with KIRA8 according to the reversal regimen. (E) Markers of fibrosis (lung weight, hydroxyproline content, collagen 1A1 mRNA, and fibronectin mRNA) from mice exposed to saline or bleomycin, and treated with KIRA8 according to the reversal regimen. Each mouse is represented by a dot, and whiskers denote group mean +/- SEM. P values: *<0.05, **<0.01, ***<0.001.