Figure 4.

In vivo pMLC2 modulation. (A) Female, 8-week-old C57/BL6 mice (n = 8 per group) were dosed with indicated amounts of BLU4565 or BLU0556, respectively. Submandibular bleeds were taken one hour after dosing, and samples were analyzed by flow cytometry. Plasma samples were also taken to measure compound exposure. For pMLC2 flow cytometry, red blood cells were lysed, lymphocytes were stained with anti-CD3, and intracellular staining for pMLC2 was performed. (B) C57BL/6 mice (n = 6 per group) were dosed with BLU7482 (200 mg/kg QD or 50 mg/kg BID). Whole blood was collected through submandibular vein at 1 or 24 hours post treatment, followed by immunostaining and FACS analysis. Plasma samples were taken at 1 and 24 hours to determine compound exposure. Representative of n=3 experiments is shown. *P=0.0178, ***P=0.0003, ****P<0.001. BID, twice a day; CD, cluster of differentiation; EC₅₀, half maximal effective concentration; IL-2, interleukin-2; MFI, mean fluorescence intensity; PD, pharmacodynamics; PK, pharmacokinetics; pMLC2, phospho-myosin light chain 2; P.O., orally; QD, daily.