Promising drug discovery strategies for sirtuin modulators: what lessons have we learnt?

Geetika Garg, Abhishek Kumar Singh, Sandeep Singh, Syed Ibrahim Rizvi

Expert opinion on drug discovery 2021 Aug

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Sirtuins, NAD-dependent protein deacetylases, require NAD+ for enzymatic activity. Recent research has indicated that sirtuins have a key role in the regulation of gene expression, the cell cycle, apoptosis, neurodegeneration and several age-related diseases. In mammals, there are seven sirtuin isoforms (SIRT-1-7) that catalyze specific lysine substrate deacetylation. This review explains the current information on the structure, function and importance of sirtuin modulators. It also explores the possible therapeutic applications of sirtuin modulators and related small molecules in the context of various diseases. Sirtuin's modulators open a new area of research for targeting pathological conditions. Sirtuin modulators, through their targeted function, may provide a possible tool for the amelioration of various diseases. However, the search of activators/inhibitors for sirtuins needs further research. The structural elucidation of sirtuins will create an understanding for the development of isoform-specific selective modulators. This could be a useful tool to determine the functions of individual sirtuins as potential therapeutic agents.

Citation

Geetika Garg, Abhishek Kumar Singh, Sandeep Singh, Syed Ibrahim Rizvi. Promising drug discovery strategies for sirtuin modulators: what lessons have we learnt? Expert opinion on drug discovery. 2021 Aug;16(8):915-927