Sirtuin modulators: an updated patent review (2012 – 2014)

Abstract

Introduction: Since 2000 sirtuins (SIRT1–7) have gained growing attention for their connections with many biological processes such as cellular metabolism regulation, neuroprotection, apoptosis, inflammation, and cancer progression. In particular, SIRT1 has been the most studied isoform, not only for its role during caloric restriction but also as target in prevention of aging-related diseases. SIRT inhibition can be useful for treating cancer, HIV infection or muscular diseases, SIRT activation can exert positive effects in aging-related disorders such as metabolism, cardiovascular, and neurodegenerative diseases.

Areas covered: This review includes the patents about sirtuin modulation released during the 2012 – 2014 period, and covers the potential therapeutic uses of known sirtuin modulators as well as new related small molecules in various disease contexts.

Expert opinion: The effective role of sirtuins in cancer is still controversial, because some of them seem to have tumor-promoter as well as tumor-suppressor properties. Thus, few patents describing SIRT inhibitors have been found in 2012 – 2014 period. Despite the still active debate on their role as direct or indirect activators of SIRT1, sirtuin-activating compounds are actually subjected to intense research for the ability to treat neurodegenerative diseases, metabolic disorders, inflammation, vascular system injuries, wound healing and endothelial dysfunctions. A great number of clinical trials are reported with either SIRT inhibitors or activators, thus it is possible that in the foreseeable future one or more of them will enter in the clinical arena.

Keywords:

• diabetes
• epigenetics
• inflammation
• obesity
• sirtuins
• small molecule activators

Declaration of interest

The authors were supported by the Italian Ministry of Health funds: FIRB RBFR10ZJQT, RF-2010-2318330, Progetto Ateneo Sapienza 2013, FP7 Projects BLUEPRINT/282510 and A-ParaDDisE/602080. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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