Discovery of novel benzimidazole derivatives as potent p300 bromodomain inhibitors with anti-proliferative activity in multiple cancer cells

Bioorg Med Chem. 2022 Jul 15:66:116784. doi: 10.1016/j.bmc.2022.116784. Epub 2022 May 1.


Adenovirus E1A-associated 300-kD protein (p300) bromodomain, which regulates gene expression by recognizing acetylated lysine (KAc) of histone, is a promising target for the treatment of cancer. Herein, a series of potent p300 bromodomain inhibitors with novel CBP30-based scaffolds was discovered through bioisosterism and conformational restriction strategies. The most promising compound 1u showed more potent inhibitory activity (IC50 = 49 nM) against p300 bromodomain and anti-proliferative activity in various cancer cell lines compared to CBP30. Moreover, 1u suppressed the expression of c-Myc and induced G1/G0 phase arrest and apoptosis in OPM-2 cells more potently than CBP30. This study provides new lead compounds for further research on the biological functions of p300.

Keywords: Bromodomain inhibitors; CBP30; P300; SBDD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Benzimidazoles / pharmacology
  • Humans
  • Neoplasms*
  • Protein Domains


  • Benzimidazoles