pp 1-38 | Cite as

Sirtuin Inhibitors and Activators

  • Minna Rahnasto-Rilla
  • Jonna Tyni
  • Maija Lahtela-Kakkonen
Part of the Topics in Medicinal Chemistry book series


The mammalian family of sirtuins (SIRT1–7) target a large variety of proteins at various subcellular localizations and thus exert regulatory effects on critical biological processes such as gene silencing, DNA repair, and chromosomal stability and longevity. Sirtuins play crucial roles in many signaling pathways and are regarded as potential therapeutic targets in several pathological conditions, such as cancer, metabolic disorders, and also cardiovascular and neurodegenerative diseases. Therefore, the modulation of sirtuin activity by inhibitors or activators could be beneficial for human health, a topic that has been interesting scientists for over 15 years. Researchers have developed novel inhibitors and activators toward sirtuins mainly for human silent information regulator type 1 (SIRT1) because both cellular studies and experiments in animal models have indicated that SIRT1 regulators could be used for the treatment for multiple human diseases. Gradually, an appreciation of the importance of the other members of the sirtuin family has increased, and potent inhibitors and activators are designed for various sirtuins.


Activation Deacetylation Drug design and development Inhibition Sirtuin 



Alzheimer’s disease


Adenosine diphosphate




Adenosine triphosphate




Carbamoyl phosphate synthetase peptides


Concentration of compound required to increase the enzyme activity by 50%


Effective concentration which increases the enzyme activity to 150%


Half maximal effective concentration


Forkhead O transcription factor 3 α


Histone H3 lysine 9


Huntington’s disease


Histone deacetylase enzymes


High-throughput screening


Half maximal inhibitory concentration




Value of substrate concentration at half maximal velocity




Manganese superoxide dismutase


Nicotinamide adenine dinucleotide




Nitric oxide


Peroxisome proliferator-activated receptor gamma coactivator 1-alpha Protein kinase C


Parkinson’s disease


Reactive oxygen species


Structure-activity relationships


Sirtuin-rearranging ligand2




Silent information regulator type 1


Sirtuin-activating compounds




Tumor necrosis factor alpha


Compliance with Ethical Standards

Funding: M.R-R. was supported by Academy of Finland (grant no. 269341), Finnish Cultural Foundation, and Maud Kuistila Memorial Foundation. J.T was supported by UEF Doctoral School.

M.L-K. was supported by Academy of Finland (grant no 315824).

Conflict of Interest: There is no conflict of interest.

Ethical Approval: This chapter does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent: This chapter does not contain any informed consent material.


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Copyright information

© Springer Nature Switzerland AG  2019

Authors and Affiliations

  • Minna Rahnasto-Rilla
    • 1
  • Jonna Tyni
    • 1
  • Maija Lahtela-Kakkonen
    • 1
  1. 1.School of Pharmacy, University of Eastern FinlandKuopioFinland

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