ZL0420

ZL0420 is an inhibitor of bromodomain 1 (BD1) and BD2 in bromodomain-containing protein 4 (BRD4; IC₅₀s = 27 and 32 nM, respectively).¹ It is selective for BD1 and BD2 in BRD4 over BD1 in BRD2, BRD3, and BRDT (IC₅₀s = 803, 2,275, and 3,183 nM, respectively) and BD2 (IC₅₀s = 1,736, 2,193, and 2,781 nM, respectively), as well as the bromodomain in CBP (IC₅₀ = >10,000 nM). ZL0420 inhibits the expression of interferon-stimulated gene 54 (ISG54), ISG56, IL-8, and growth-regulated protein β (Groβ) induced by the toll-like receptor 3 (TLR3) agonist poly(I:C) by approximately 95% in human small airway epithelial cells. It also inhibits neutrophil infiltration around small- and medium-sized airways and reduces cytokine expression in lung tissue in a poly(I:C)-induced mouse model of acute airway inflammation when administered at a dose of 10 mg/kg.

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1. Liu, Z., Tian, B., Chen, H., et al. Discovery of potent and selective BRD4 inhibitors capable of blocking TLR3-induced acute airway inflammation. Eur. J. Med. Chem. 151, 450-461 (2018).