BAL-0598 inhibits NLRP3 in vivo. (A) Schematic illustration of peritonitis model and BAL-0598 dosing. (B and C) Levels of IL-1β (B) and IL-6 (C) in the PLF of 129S6 mouse promoter-NLRP3 mice after peritonitis induced by LPS and ATP in the presence of increasing amounts of BAL-0598. Graph symbols show values from individual mice ± SD. (D) Average IL-1β release values ± SD in PLF from mice treated with BAL-0598 prior to peritonitis, and ED₅₀ curve was fitted by nonlinear regression analysis. (E) Total plasma BAL-0598 levels from BAL-0598 oral gavage-treated mice. Graph symbols show values from individual mice ± SD. N = 8–10 mice per group (B–E). (F) IL-1β release values in PLF from 44 individual mice treated with BAL-0598 prior to peritonitis plotted against corresponding plasma levels of unbound BAL-0598, and IC₅₀ and IC₉₀ curves were fitted by nonlinear regression analysis. (B and C) Data were compared using a Kruskal–Wallis test with Dunn’s multiple comparisons test. ***P ≤ 0.001; ****P ≤ 0.0001.