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

Shipeng He, Guoqiang Dong, Yu Li, Shanchao Wu, Wei Wang, Chunquan Sheng

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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. Reported here is a new, effective therapeutic strategy and the design of small-molecule inhibitors that simultaneously target bromodomain and extra-terminal (BET) and histone deacetylase (HDAC), potentially serving as promising therapeutic agents for pancreatic cancer. A highly potent dual inhibitor (13 a) is identified to possess excellent and balanced activities against BRD4 BD1 (IC50=11 nm) and HDAC1 (IC50=21 nm). Notably, this compound shows higher in vitro and in vivo antitumor potency than the BET inhibitor (+)-JQ1 and the HDAC inhibitor vorinostat, either alone or and in combination, highlighting the advantages of BET/HDAC dual inhibitors for more effective treatment of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)3028-3032
Number of pages5
JournalAngewandte Chemie - International Edition
Volume59
Issue number8
DOIs
StatePublished - Feb 17 2020
Externally publishedYes

Keywords

  • anticancer
  • antitumor agents
  • drug discovery
  • heterocyles
  • inhibitors

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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