Balsalazide-Derived Heterotriaryls as Sirtuin 5 Inhibitors: A Case Study of a Reversible Covalent Inhibition Strategy.

ABSTRACT: Sirtuin 5 is an NAD⁺-dependent lysine deacylase that is involved in various biological processes and has emerged as a promising target for pharmaceutical therapies. The development of highly potent and subtype-selective sirtuin 5 inhibitors for their application as chemical tools and drug candidates still poses a significant challenge. Based on our own optimized balsalazide-derived sirtuin 5 inhibitors, this work presents a systematic investigation of the inhibitory effects of derivatives with moieties that were guided by docking experiments to target the nicotinamide ribose vicinal hydroxy groups of the essential co-factor NAD⁺ via reversible covalent binding to potentially enhance their potency. Our results show that functionalizations with these moieties were toler

SUBMITTER: Wirawan R 

PROVIDER: S-EPMC12472749 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature