Symmetrical 2,7-disubstituted 9H-fluoren-9-one as a novel and promising scaffold for selective targeting of SIRT2.

ABSTRACT: Sirtuin 2 (SIRT2) belongs to the family of silent information regulators (sirtuins), which comprises nicotinamide adenine dinucleotide (NAD⁺)-dependent protein lysine deacetylases. With a distribution across numerous tissues and organs of the human body, SIRT2 is involved in a wide range of physiological and pathological processes, such as regulating the cell cycle, energy metabolism, DNA repair, and tumorigenesis. Aberrant expression of SIRT2 has been closely associated with particular etiologies of human diseases, positioning SIRT2 as a promising therapeutic target. Herein, we detail the design overview and findings of novel symmetrical 2,7-disubstituted 9H-fluoren-9-one derivatives targeting SIRT2. SG3 displayed the most potent SIRT2-selective inhibitory profile, with an IC

SUBMITTER: Kaya SG 

PROVIDER: S-EPMC11610652 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature