Open AccessEmerging Therapeutic Potential of SIRT6 Modulators
Author(s) -
Francesco Fiorentino,
Antonello Mai,
Dante Rotili
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.1c00601
Subject(s) - sirtuin , sirt6 , nad+ kinase , chemistry , context (archaeology) , enzyme , pharmacology , cancer research , biochemistry , biology , paleontology
Sirtuin 6 (SIRT6) is an NAD + -dependent protein deacylase and mono-ADP-ribosyltransferase of the sirtuin family with a wide substrate specificity. In vitro and in vivo studies have indicated that SIRT6 overexpression or activation has beneficial effects for cellular processes such as DNA repair, metabolic regulation, and aging. On the other hand, SIRT6 has contrasting roles in cancer, acting either as a tumor suppressor or promoter in a context-specific manner. Given its central role in cellular homeostasis, SIRT6 has emerged as a promising target for the development of small-molecule activators and inhibitors possessing a therapeutic potential in diseases ranging from cancer to age-related disorders. Moreover, specific modulators allow the molecular details of SIRT6 activity to be scrutinized and further validate the enzyme as a pharmacological target. In this Perspective, we summarize the current knowledge about SIRT6 pharmacology and medicinal chemistry and describe the features of the activators and inhibitors identified so far.