Histological analysis of isolated tissues from APAP-treated mice demonstrated that all compounds, except I-BET151, were effective at reducing necrosis (Figure ). Neutrophil infiltration was assessed based on analysis of neutrophil marker, Ly6G (Figure ), as well as MPO staining of tissue as an orthogonal analysis (Figure ). Reduction of these neutrophil markers was not significant; however, these data cannot rule out recruitment at other timepoints. Together, these results demonstrate that both pan-BET inhibitors and pan-D1 biased inhibitors are effective at significantly reducing liver inflammation induced by LPS administration and APAP-induced toxicity via reducing chemokine expression and cellular necrosis, but only with minor effects on neutrophil recruitment under the conditions tested. BRD4-D1 selective inhibitors can also reduce necrosis and have a mild effect on neutrophil recruitment, however improved inhibitors with optimized drug-like properties will be necessary to evaluate their efficacy in vivo.