selisistat (SEN-196)

We found that increased serum sST2 levels were significantly correlated with the progression of adverse ventricular remodeling following MI. Furthermore, our study provides the first preclinical evidence demonstrating that TMPZ attenuates this remodeling process by targeting the Sirt1/p300/Yy1/sST2 signaling axis. Collectively, these findings not only highlight sST2 as a promising therapeutic target but also establish a mechanistic rationale for developing novel interventions through pharmacological modulation of the Sirt1/sST2 pathway.

Preclinical studies show that pharmacological inhibition of SIRT1 (e.g., with EX-527 or cambinol) restores chemosensitivity and reduces tumor cell viability, suggesting potential for SIRT1 inhibitors as adjuncts in cancer therapy...Further investigation is needed to define therapeutic windows, molecular contexts, and combination strategies that could optimize SIRT1-targeted therapies. This review summarizes the current understanding of SIRT1's roles in breast and gynecologic malignancies.

The selective SIRT1 inhibitor EX-527 abrogated both the anti-liver injury and anti-fibrotic effects of MCL...MCL mitigates CCl4-induced liver injury and fibrosis by activating SIRT1 to suppress liver inflammation in mice. These findings uncover a novel molecular mechanism for the anti-liver fibrotic activity of MCL and highlight its potential as a therapeutic candidate for liver fibrosis.

In this study, we first probed into the effect of sirtuin 1 inhibitor III (EX527) on hepatitis B virus (HBV) replication following inhibition of silencing information regulator 1 (SIRT1) and whether EX527 can enhance the efficacy of entecavir (ETV) in anti-HBV therapy. SIGNIFICANCE STATEMENT: This study has important theoretical and practical significance. It explores the factors influencing the replication of the hepatitis B virus from a new perspective and provides new ideas for follow-up research.

Our study demonstrated that NR mitigates IR by inhibiting GSDME-mediated pyroptosis and restoring IECs homeostasis. These findings suggest that NR could serve as a promising therapeutic strategy for IR following radiotherapy.

VSL#3 balanced gut microbiota and suppressed neuroinflammation in hippocampal CA1 region by activating the AMPK/SIRT1 pathway, thereby alleviating POCD in aged mice.

The findings indicate that EA ameliorates depression-like behavior by enhancing oligodendrocyte maturation and myelin repair via activating SIRT1 signaling. These findings provide novel mechanistic insights into non-pharmacological interventions for depression.

Subsequently, EX-527, a selective SIRT1 inhibitor, was used for inhibiting SIRT1, and it reversed the protective effect of TRL in SAKI...Therefore, TRL may be a potential therapeutic approach for SAKI treatment. Key words Trigonelline " Sepsis-induced acute kidney injury " NAD+ " SIRT1.

Vitexin ameliorates CIRI by activating mitophagy via the SIRT1/PINK1/Parkin pathway.

The lung pathology in EX527-treated group with infection was strongly associated with the BAL Ly6G+TNF-α+ cells and the Sirt1 levels in Ly6Ghi neutrophils. Overall, the results showed that although the Sirt1 activator had a greater effect in normalizing the BM and blood neutrophils in severe IAV infection, its effectiveness was compromised locally by its failure to inhibit the expanded neutrophil pools to a degree that was less detrimental.

HucMSC-Ex alleviates IBD by reducing the acetylation level of FXR through activating the SIRT1-FXR pathway in macrophages and directly negatively regulating the activation of NLRP3 inflammasomes, thus inhibiting the occurrence of the inflammatory process.

Myocardial ischemia-reperfusion injury (MIRI) significantly affects the prognosis of cardiac surgery patients. These protective effects were markedly reversed by EX527. These findings indicate that Dex alleviates MIRI by restoring Sirt1 expression and activating FoxO3a.