DW34 is an orally bioactive pan-BRD4-D1-biased inhibitor that also exhibits BRD4-D2 activity. It demonstrates a low nanomolar inhibitory effect comparable to I-BET151 (EC50 value of 0.16 μM), with an EC50 value of 0.14 μM. DW34 significantly alleviates lipopolysaccharide (LPS)-induced liver inflammation and acetaminophen (APAP)-induced toxicity by reducing chemokine expression and cell necrosis.

DW34 (Compound 3) effectively inhibits the expression of CXCL1 and CCL2 in LPS-induced transformed sinusoidal endothelial cells (TSECs) at concentrations of 0.31-5 μM over 5 hours. At 0.5-5 μM over 2 hours, DW34 demonstrates a stabilization effect on BRD4 in HEK293T cells comparable to I-BET151. Furthermore, DW34 exhibits good tolerance in transformed sinusoidal endothelial cells (TSECs) at concentrations ranging from 0.1 to 200 μM over 4 hours. It also induces a toxic response in megakaryocytes with an EC50 value of 90 nM.

When administered orally at 30 mg/kg for durations of 9 or 12 hours, DW34 effectively reduces LPS-induced liver inflammation and APAP-induced toxicity by decreasing chemokine expression and cellular necrosis.