ZL0420

ZL0420 is a potent and selective bromodomain-containing protein 4 (BRD4) inhibitor with IC₅₀ values of 27 nM against BRD4 BD1 and 32 nM against BRD4 BD2. IC50 & Target:IC50: 27 nM (BRD4 BD1), 32 nM (BRD4 BD2)^[1] In Vitro: ZL0420 is well docked into the acetyl-lysine (KAc) binding pocket of BRD4, forming key interactions including the critical hydrogen bonds with Asn140 directly and Tyr97 indirectly via a H₂O molecule. ZL0420 exhibits submicromolar potency of inhibiting the TLR3-dependent innate immune gene program, including ISG54, ISG56, IL-8, and Groβ genes in cultured human small airway epithelial cells (hSAECs) with IC₅₀s of 0.49-0.86 µM^[1]. In Vivo: ZL0420 demonstrates potent efficacy reducing airway inflammation in a mouse model with low toxicity. ZL0420 displays high efficacy and almost completely blocks the profound accumulation of neutrophils around the small and medium sized airways induced by poly(I:C) administration^[1].