Highly Potent Dual BET/HDAC Inhibitors for the Efficient Treatment of Pancreatic Cancer.

Highly Potent Dual BET/HDAC Inhibitors for the Efficient Treatment of Pancreatic Cancer. Angew Chem Int Ed Engl. 2020 Jan 14;: Authors: Wang W, He S, Dong G, Li Y, Wu S, Sheng C Abstract As one of the most aggressive and lethal human malignancies with extremely poor prognosis, there is an urgent demand of more effective therapy for the treatment of pancreatic cancer. Herein we wish to report a new, effective therapeutic strategy that small molecule inhibitors simultaneously targeting bromodomain and extra-terminal (BET) and histone deacetylase (HDAC) are rationally designed as promising therapeutic agents for pancreatic cancer. A highly potent dual inhibitor ( 13a ) is identified to possess excellent and balanced activities against BRD4 BD1 (IC 50 = 11 nM) and HDAC1 (IC 50 = 21 nM). Notably, this compound shows higher in vitro and in vivo antitumor potency than BET inhibitor (+)-JQ1, HDAC inhibitor vorinostat and their combination, highlighting the advantages of BET/HDAC dual inhibitors for the more effective treatment of pancreatic cancer. PMID: 31943585 [PubMed - as supplied by publisher]
Source: Angewandte Chemie - Category: Chemistry Authors: Tags: Angew Chem Int Ed Engl Source Type: research