OSS_128167

OSS_128167 (CAS No.: 887686-02-4) is a selective small-molecule inhibitor of sirtuin 6 (SIRT6), a NAD+-dependent histone deacetylase implicated in chromatin remodeling, metabolic regulation, inflammation, and aging-related pathways. It exhibits preferential inhibition of SIRT6 over other sirtuin isoforms, with activity observed in the low micromolar range for SIRT6 and substantially weaker inhibition of SIRT1 and SIRT2, supporting its utility as a tool compound for dissecting SIRT6-specific biological functions. Mechanistically, OSS_128167 suppresses SIRT6 enzymatic activity, leading to increased acetylation of histone H3 lysine 9 and modulation of downstream gene expression, and has been shown to influence cellular processes such as glucose uptake and inflammatory cytokine production. In virological contexts, it inhibits hepatitis B virus transcription and replication through SIRT6-dependent mechanisms, highlighting its relevance in host–virus interaction studies. Additionally, it demonstrates anti-inflammatory effects by reducing pro-inflammatory mediators and has shown activity in cancer-related cellular models, indicating broader applications in oncology and immunology research. In vivo studies further suggest neuroprotective and anti-inflammatory potential in models of cerebral injury, including attenuation of cytokine release and immune cell infiltration. OSS_128167 is widely used in biochemical and cell-based assays to investigate SIRT6-associated signaling pathways, epigenetic regulation, and disease mechanisms, with experimental concentrations and dosing regimens tailored to specific study designs.