We next assessed the activity of our compounds in an LPS-induced model of inflammatory signaling in transformed liver sinusoidal endothelial cells (TSECs). We chose an endothelial cell line because liver sinusoidal endothelial cells are an important source of chemokines and cytokines in vivo. To determine optimal concentrations, we tested our compounds in an XTT cytotoxicity assay. In this case, I-BET151, iBETBD2, 2, and 3 were well tolerated. However, 1 showed reduced viability at concentrations above 10 μM. Having established a maximum dose of our compounds which is minimally toxic, we next measured the inhibitory effects on CXCL1 and CCL2 expression upon LPS stimulation using three concentrations: 0.3, 1.25, and 5 μM (Figure , Figure ). Our results were consistent with prior reports where I-BET151 downregulated both chemokines. Inhibitors 1, 2, and 3 all inhibited both CXCL1 and CCL2 expression, with 3 showing levels of expression comparable to I-BET151. Surprisingly, pan-D2 inhibitor, iBETBD2, was less effective than either 3 or IBET-151 in regulating CCL2 expression, despite its activity in other models of inflammation. 32 BRD4-D1 selective inhibitors 1 and 2 had similar to slightlyimproved activity compared to iBETBD2's effects on both CXCL1 and CCL2 expression. Notably, cellular toxicity led to an increase in chemokine expression at the highest concentrations tested for these two inhibitors (Figure ).