Identification of small molecules that activate human endothelial cells. (A) IFNγ (10 ng/mL), DMSO controls (n = 60 total replicates), and 642 compounds (10 μM) were tested for their ability to promote MIP1β production. The library contained 37 compounds capable of inducing MIP1β at least to the level of IFNγ (red dashed line). * represents five distinct scaffolds with activity, whereas ** represents the two naphtyridine families. (B) Structures of five octahydronaphthyridinones selected for further study. (C) Confirmation of a subset of active compounds: Coculture is required for MIP1β production. Data represents mean ± SEM of triplicate wells from one of two comparable experiments. # p values for MIP1β: (a) 105A3 = 0.008, (b) A8 = 0.003, (c) A10 = 0.026, (d) A11 = 0.007, and (e) B2 = 0.046. ## p values for MIP1α: (a) 105A3 = 0.042, (b) A8 = 0.016, (c) A10 = 0.009, (d) A11 = 0.041, and (e) B2 = 0.13. (D) Activated endothelium triggers MIP1β production from CD14+ monocytes. Percent positive MIP1β cells and mean fluorescence intensity (MFI) of MIP1β+ cells are shown.