# Recent Advances in the Discovery of SIRT1/2 Inhibitors via Computational Methods: A Perspective

## TL;DR

This paper reviews recent computational methods used to discover inhibitors for SIRT1 and SIRT2 enzymes, which are linked to various diseases.

## Contribution

The paper provides a comprehensive overview of computational approaches and recent SIRT1/2 inhibitors identified since 2017.

## Key findings

- Computational methods have successfully identified novel and selective SIRT1/2 inhibitors.
- A variety of SIRT–ligand complexes have been elucidated, aiding inhibitor discovery.
- Recent literature highlights promising SIRT1/2 inhibitors with potential therapeutic applications.

## Abstract

Sirtuins (SIRTs) are classified as class III histone deacetylases (HDACs), a family of enzymes that catalyze the removal of acetyl groups from the ε-N-acetyl lysine residues of histone proteins, thus counteracting the activity performed by histone acetyltransferares (HATs). Based on their involvement in different biological pathways, ranging from transcription to metabolism and genome stability, SIRT dysregulation was investigated in many diseases, such as cancer, neurodegenerative disorders, diabetes, and cardiovascular and autoimmune diseases. The elucidation of a consistent number of SIRT–ligand complexes helped to steer the identification of novel and more selective modulators. Due to the high diversity and quantity of the structural data thus far available, we reviewed some of the different ligands and structure-based methods that have recently been used to identify new promising SIRT1/2 modulators. The present review is structured into two sections: the first includes a comprehensive perspective of the successful computational approaches related to the discovery of SIRT1/2 inhibitors (SIRTIs); the second section deals with the most interesting SIRTIs that have recently appeared in the literature (from 2017). The data reported here are collected from different databases (SciFinder, Web of Science, Scopus, Google Scholar, and PubMed) using “SIRT”, “sirtuin”, and “sirtuin inhibitors” as keywords.