A Bromodomain-Containing Protein 4 (BRD4) Inhibitor Suppresses Angiogenesis by Regulating AP-1 Expression.

ABSTRACT: Angiogenesis dysregulation contributes to inflammation, infections, immune disorders, and carcinogenesis. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader that recognizes histone proteins and acts as a transcriptional regulator to trigger tumor growth and the inflammatory response. The pan-bromodomain and extra-terminal domain (BET) inhibitor, (+)-JQ1 (1), was reported to inhibit angiogenesis. However, owing to the non-selectivity action of (+)-JQ1 towards all BET family members, the role of BRD4 and that of its bromodomains (BD1 and BD2) in angiogenesis remains elusive. Herein, we identified a potent BRD4 inhibitor, ZL0513 (7), which exhibited significant anti-angiogenic effects in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models.

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC7381267 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature