Related Experiment Video

Updated: Aug 23, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins (SIRT2) and Specific Protein-substrates

Published on: February 27, 2016

Targeting SIRT6: the design and therapeutic implications of activators and inhibitors

Yuxin Shi1, Xiaofan Han1, Xinqi Li1

  • 1Department of Medicinal Chemistry, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, Shandong Basic Science Academic Special Zone/ Research Center (Pharmacy), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China.

Bioorganic & Medicinal Chemistry
|August 21, 2026
PubMed

Insights

Sirtuin 6 (SIRT6) is a key enzyme for genomic stability and metabolism. Medicinal chemistry advances offer new SIRT6 modulators for treating cancer and metabolic disorders.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Molecular Biology

Background:

  • Sirtuin 6 (SIRT6) is an NAD+-dependent deacylase crucial for genomic stability, metabolism, and aging.
  • Its complex roles make it a promising therapeutic target for cancer and metabolic diseases.
  • Precise pharmacological modulation is needed due to SIRT6's context-dependent functions.

Purpose of the Study:

  • To review recent medicinal chemistry progress in developing Sirtuin 6 (SIRT6) modulators.
  • To evaluate structure-guided design and structure-activity relationships (SAR) for SIRT6 activators and inhibitors.
  • To identify challenges in achieving isoform selectivity and drug-like properties for SIRT6-targeted therapies.

Main Methods:

  • Critical evaluation of recent medicinal chemistry literature on SIRT6 modulators.
  • Focus on structure-activity relationships (SAR) and structure-guided design strategies.
  • Analysis of chemical probes for dissecting SIRT6 biology and therapeutic potential.

Main Results:

  • Significant advances have been made in transforming initial SIRT6 hits into optimized lead compounds.
  • Structure-activity relationships (SAR) have been elucidated for both SIRT6 activators and inhibitors.
  • Development of potent, selective, and drug-like chemical probes is progressing.

Conclusions:

  • Medicinal chemistry efforts have yielded promising SIRT6 modulators for therapeutic applications.
  • Further research is needed to address challenges in isoform selectivity and to optimize drug-like properties.
  • SIRT6 chemical probes are essential tools for understanding its biology and validating therapeutic strategies.
Keywords:
ActivatorDeacetylaseInhibitorSIRT6

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