ZL0420 is a potent and selective bromodomain-containing protein 4 ( BRD4 ) inhibitor with nanomolar binding affinities to bromodomains (BDs) of BRD4. ZL0420 has IC 50 values of 27 nM against BRD4 BD1 and 32 nM against BRD4 BD2.

ZL0420有效地结合到BRD4的乙酰化赖氨酸(KAc)结合口袋中，形成关键相互作用，包括通过一分子H2O间接与Tyr97建立的关键氢键和直接与Asn140的关键氢键。ZL0420在抑制TLR3依赖的天然免疫基因程序方面展现出亚μM级别的效力，这包括在培养的人类小气道上皮细胞(hSAECs)中抑制ISG54、ISG56、IL-8和Groβ基因，IC50值为0.49-0.86μM[1]。

ZL0420在低毒性条件下显著有效降低小鼠模型的气道炎症。ZL0420具有高度的效力，几乎完全阻断了由poly(I:C)给药引起的中小型气道周围中性粒细胞的大量积聚[1]。

Male C57BL6/J mice housed under pathogen-free conditions with food and water ad libitum.?C57BL/6 mice were pre-treated in the absence or presence of the indicated BRD4 inhibitors [10 mg/kg body weight, via the intraperitoneal route] one day prior to poly stimulation.?The next day, animals were given another dose of BRD4 inhibitor immediately followed by intranasal ?administration of phosphate-buffered saline (PBS, 50 μL) or poly (300 μg dissolved in 50 μL PBS).?One day later, the mice were euthanized.?The bronchoalveolar lavage fluid (BALF) and lung tissues of treated mice were collected for further analysis.?Compounds were first dissolved in DMSO and further diluted in 10% hydroxypropyl β-cyclodextrin in PBS to appropriate concentration prior to intraperitoneal administration.