Skip to main content
. 2023 Aug 9;14:4812. doi: 10.1038/s41467-023-40536-y

Fig. 5. Washout PK/PD demonstrates different pharmacological profiles of thiazole and thiophene BDK inhibitors.

Fig. 5

Mice were fed HFD for 10 weeks, at which time animals were randomized into groups, and treated BID or QD as indicated with vehicle, BT2, PF-07208254, PF-07247685, or PF-07238025 at maximal inhibitory doses. A Study design. Mice were bled immediately prior to dosing compound, 1 h post compound dose, 4 h post compound dose, 7 h post compound dose (immediately prior to 2nd daily compound dose if BID dosed), and 24 h after first compound dose on day 3 and day 17 (N = 8–9 animals/group; a longitudinal mixed effects model with an unstructured covariance was used for statistics for C–D, F–G). B After the final compound dose on day 19, animals were bled at 24 h, 36 h, 45 h, and 68 h on days 20–21 (N = 5 animals/group; a longitudinal mixed effects model with a random intercept for each mouse and an AR(1) covariance structure was fit for statistics for E, H). C Leucine was measured on day 3, (D) day 17 (*p = 0.043, **p = 0.01, ***p = 0.001, #p < 0.0001, +within group, p = 0.049 from day 3), and (E) upon compound washout (*p = 0.047, 0.013). F Ketoleucine was measured on day 3, (G) day 17 (#p < 0.0001, ++ within group, p < 0.001 from day 3), and (H) upon compound washout (#p < 0.0001, ***p = 0.001). Dashed lines in panels E, H represent the 0–7 h time points from D and G for visualization purposes. Data represent the mean ± SEM. Source data are provided as a Source Data file.