Recent Advances in Inhibitors of sirtuin1/2: An Update and Perspective

Future Med Chem. 2018 Apr 1;10(8):907-934. doi: 10.4155/fmc-2017-0207. Epub 2018 Apr 12.


Sirtuins (SIRT) are coenzyme NAD+-dependent histone deacetylases for the transfer of modified acetyl groups. Sirtuins are widely involved in various physiological processes and therefore associated with cardiovascular disease, diabetes, Parkinson's disease, cancer and beyond. Consequently, the development of modulators for sirtuins has considerable clinical value. To date, a variety of SIRT1/2 inhibitors have been reported and none has been approved for the market. This review summarizes the recent progress in the discovery and development of SIRT1/2 inhibitors including their inhibitory potency, structure-activity relationship and binding mode analysis as well as discusses the perspective for the future development of SIRT1/2 inhibitors.

Keywords: SIRT1; SIRT2; inhibitors; progress; sirtuins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Discovery* / methods
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Molecular Docking Simulation
  • Neoplasms / drug therapy
  • Parkinson Disease / drug therapy
  • Sirtuin 1 / antagonists & inhibitors*
  • Sirtuin 1 / metabolism
  • Sirtuin 2 / antagonists & inhibitors*
  • Sirtuin 2 / metabolism
  • Structure-Activity Relationship


  • Histone Deacetylase Inhibitors
  • Sirtuin 1
  • Sirtuin 2