Pharmacogenomic profiling and virtual screening revealed macitentan as a potent inhibitor of the integrin α9/VCAM-1 interaction. (A) The top 10 concordant perturbagens with concordance scores >0.321 are shown using iLINCS portal based on RNA-seq of neutrophils of littermate controls and neutrophil–specific integrin α9^−/− mice. (B) The template (green, α4 subunit) and target (cyan, α9 subunit) models. (C) The predicted α9β1 structure with an inhibitor. (D) List of top-19 compounds with binding energy and percentage inhibition of integrin α9 to VCAM-1. (E) Chemical structure of macitentan. (F) Docked pose of macitentan with integrin α9β1. (G) Representative images of neutrophil adhesion to VCAM-1 in presence of different concentration of macitentan (left); magnification, 10×; scale bar, 100 μm; and quantification (right). (H) Representative images of the mouse neutrophil adhesion to the activated mouse venous endothelial cells coated slides at venous shear rate (left); magnification, 20×; scale bar, 50 μm; and qualification (right). Data are mean ± SEM and analyzed by 1-way ANOVA followed by Sidak multiple comparisons test (G) or Mann-Whitney test (H); n = 6 (G); and n = 5 (H).