Current development of CBP/p300 inhibitors in the last decade

Eur J Med Chem. 2021 Jan 1:209:112861. doi: 10.1016/j.ejmech.2020.112861. Epub 2020 Oct 1.


CBP/p300, functioning as histone acetyltransferases and transcriptional co-factors, represents an attractive target for various diseases, including malignant tumor. The development of small-molecule inhibitors targeting the bromodomain and HAT domains of CBP/p300 has aroused broad interests of medicinal chemist in expectation of providing new hope for anti-cancer treatment. In particular, the CBP/p300 bromodomain inhibitor CCS1477, identified by CellCentric, is currently undergone clinical evaluation for the treatment of haematological malignancies and prostate cancer. In this review, we depict the development of CBP/p300 inhibitors reported from 2010 to 2020 and particularly highlight their structure-activity relationships (SARs), binding modes, selectivity and pharmacological functions with the aim to facilitate rational design and development of CBP/p300 inhibitors.

Keywords: Bromodomain; CBP/p300; HAT; Inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Histone Acetyltransferases / antagonists & inhibitors*
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / metabolism
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Protein Domains / drug effects
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • p300-CBP Transcription Factors / antagonists & inhibitors*
  • p300-CBP Transcription Factors / chemistry
  • p300-CBP Transcription Factors / metabolism


  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors