ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma

Bromodomain-that contains protein 4 (BRD4) is overexpressed in thyroid carcinoma, represents being an important therapeutic target. ARV-825 is really a novel cereblon-based PROTAC (Proteolysis Targeting Chsimera) compound. It may induce fast and sustained BRD4 protein degradation. Its potential effect in human thyroid carcinoma cells was studied here. In TPC-1 cells and first human thyroid carcinoma cells, ARV-825 potently inhibited cell viability, proliferation and migration. In addition, ARV-825 caused robust apoptosis activation within the thyroid carcinoma cells. ARV-825 caused BRD4 protein degradation and downregulation of their targets, including c-Myc, Bcl-xL and cyclin D1 in thyroid carcinoma cells. It had been considerably stronger in inhibiting thyroid carcinoma cells compared to known small molecule BRD4 inhibitors. In vivo studies shown that ARV-825 dental administration potently covered up TPC-1 xenograft tumor development in severe combined immunodeficient rodents. BRD4 protein degradation in addition to c-Myc, Bcl-xL and cyclin D1 downregulation were detected in ARV-825-treated TPC-1 tumor tissues. Taken together, ARV-825 induces BRD4 protein degradation and inhibits thyroid carcinoma cell development in vitro as well as in vivo.