ZL0420 is a potent and selective bromodomain-containing protein 4 ( BRD4 ) inhibitor with IC 50 values of 27 nM against BRD4 BD1 and 32 nM against BRD4 BD2.
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 H 2 O 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 IC 50 s of 0.49-0.86 µM. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only.