Sirtuin modulators: where are we now? A review of patents from 2015 to 2019

ABSTRACT

In recent years, sirtuins (SIRTs) gained an increasing consideration because of their multiple key roles in several biological settings such as the regulation of transcription, energetic metabolism, cell cycle progression, and cytodifferentiation, apoptosis, neuro- and cardio-protection, inflammation, cancer onset and progression. Since there is mounting evidence in favor of potential therapeutic applications of SIRT modulators in various age-related disorders, the search about them is quite active.

Areas covered: This review includes the patents regarding SIRT modulators released from 2015 to 2019 and provides an overview of the most relevant SIRT modulators.

Expert opinion: Despite the knowledge about this family of broad-spectrum protein lysine deacylases has recently massively increased, there are still open questions, first of all, the exact nature of their involvement in various age-related conditions. The search for isoform-specific SIRT activators and inhibitors is still at its infancy, a limited number of patents describing them has been released, and not many clinical trials are ongoing. However, it is extremely likely that the successes obtained in the structural elucidation and structure-based design approaches that very recently have led to potent and specific SIRT modulators will pave the way for the development of further compounds selective for every single isoform.

KEYWORDS:

• Epigenetics
• sirtuins
• aging
• cancer
• neurodegeneration
• small molecule modulators

Article highlights

• Recent literature overview of NAD⁺-dependent protein lysine deacylases called sirtuins (SIRTs) and their evaluation as potential therapeutic targets via specific SIRT modulators.

• The production of patents in the field of SIRT modulators in the period 2015-2019 was analyzed.

• The activity of new SIRT inhibitors (SIRTi) and activators (SIRTa) was evaluated and found to be a potential weapon for the treatment of age-related diseases.

In the last years, just a few novel structures were patented as SIRTi or SIRTa underlining the need of pronounced efforts to discover isoform-selective modulators.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a co-inventor of a patent concerning sirtuin modulators (WO2019,162911). All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by PRIN 2016 (prot. 20152TE5PK) (A Mai), Ricerca Finalizzata 2013 PE-2013-02355271 (A Mai), AIRC 2016 (n. 19162) (A Mai), Progetto di Ateneo ‘Sapienza’ 2017 n. RM11715C7CA6CE53 (D Rotili), and NIH (n. R01GM114306) (A Mai).