(A) Schematic illustrating the timelines for in vivo administration of single-dose bleomycin and APTO-253 in a transient model of lung fibrosis and the determination of experimental endpoints at peak fibrosis (day 21). (B and C) Effect of APTO-253 administration in mice treated with and without bleomycin, as reflected by Masson’s trichrome staining for collagen deposition (stains blue) (B) and changes in the lung hydroxyproline content (C). (D) Schematic illustrating the timelines for in vivo administration of bleomycin in a 3-dose model characterized by persistent fibrosis and administration of APTO-253 during the fibrotic phase of this model beginning at day 42 and continuing until harvest at day 63. Effect of APTO-253 administration in mice treated with and without repeated bleomycin challenge, as reflected by changes in body weight (E), lung hydroxyproline content (F), Masson’s trichrome staining for collagen deposition (stains blue) (G), and expression of fibrotic markers Ctgf in whole lung tissue (H) and α-Sma in fibroblasts outgrown from lung tissue (I). Images in B and G are at original magnification of 40×, scale bar = 300 μm. In C, E, F, and H and I, each symbol represents an individual mouse. Results are expressed as mean ± SEM, n = 5–8 mice per group. *P < 0.05, 2-way ANOVA with Tukey’s multiple comparisons test.