Sirtuin activators and inhibitors: Promises, achievements, and challenges

Pharmacol Ther. 2018 Aug:188:140-154. doi: 10.1016/j.pharmthera.2018.03.004. Epub 2018 Mar 22.


The NAD+-dependent protein lysine deacylases of the Sirtuin family regulate various physiological functions, from energy metabolism to stress responses. The human Sirtuin isoforms, SIRT1-7, are considered attractive therapeutic targets for aging-related diseases, such as type 2 diabetes, inflammatory diseases and neurodegenerative disorders. We review the status of Sirtuin-targeted drug discovery and development. Potent and selective pharmacological Sirt1 activators and inhibitors are available, and initial clinical trials have been carried out. Several promising inhibitors and activators have also been described for other isoforms. Progress in understanding the mechanisms of Sirtuin modulation by such compounds provides a rational basis for further drug development.

Keywords: Activation; Deacetylase; Deacylase; Drug discovery and development; Inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Catalysis
  • Drug Development
  • Humans
  • Resveratrol / pharmacology
  • Sirtuins / antagonists & inhibitors
  • Sirtuins / chemistry
  • Sirtuins / physiology*


  • Sirtuins
  • Resveratrol