selisistat (SEN-196) / AOP Orphan Pharma - LARVOL DELTA

Celastrol Activates SIRT1/PGC-1α/Nrf2 Axis to Inhibit Oxidative Damage for Subconjunctival Fibrosis Alleviation. (PubMed, Invest Ophthalmol Vis Sci) - "The critical involvement of the SIRT1/PGC-1α/Nrf2 axis was definitively established through pharmacological inhibition using EX527, a selective SIRT1 antagonist...The results of immunofluorescence and Western blot showed that Cel inhibited subconjunctival fibrosis by activating SIRT1/PGC-1α/Nrf2 axis and suppressing TGF-β1/Smad2/3 pathway, while the SIRT1 inhibitor eliminated the effects of Cel. This work demonstrated that Cel effectively alleviated subconjunctival fibrosis by inhibiting oxidative damage via activating SIRT1/PGC-1α/Nrf2 signaling pathway, providing a new potential mechanism to clarify Cel as a potential therapeutic drug to inhibit subconjunctival fibrosis."

Journal • Fibrosis • Immunology • Ophthalmology • TGFB1

Pure platelet-rich plasma delays intervertebral disc degeneration by activating SIRT1-mediated autophagy in nucleus pulposus cells. (PubMed, J Orthop Surg Res) - "P-PRP protected against degenerative NPCs by activating functional autophagic flux and restoring mitochondrial function via the SIRT1 signaling axis. These findings provide novel mechanistic insight into PRP-based therapies and identify SIRT1 as a promising target for the treatment of IVDD."

Journal • Metabolic Disorders • ANXA5 • BECN1 • IL1B

Effect of moxibustion on SIRT1/eNOS signaling pathway in ApoE-/- atherosclerotic mice (PubMed, Zhen Ci Yan Jiu) - "Moxibustion can reduce vascular endothelial injury, improve endothelial function and promote endothelial repair in AS mice, which may be related to its function in regulating the SIRT1/eNOS signaling pathway."

Journal • Preclinical • Atherosclerosis • Cardiovascular • APOE • EDN1 • EMCN • NOS3

Metformin alleviates lung ischemia‑reperfusion injury via the SIRT1 pathway following lung transplantation in diabetic rats. (PubMed, Mol Med Rep) - "However, EX527 inhibited the protective effect of metformin. In conclusion, metformin alleviated the inflammatory response, oxidative stress and cell apoptosis, preserved mitochondrial function, and promoted mitochondrial biogenesis via the activation of the SIRT1 pathway in diabetic lung IR injury."

Journal • Preclinical • Cardiovascular • Diabetes • Inflammation • Metabolic Disorders • Reperfusion Injury • Transplantation

AMPK/SIRT1/GPX4 signaling pathway mediates the protective effect of puerarin against LPS-induced endometritis in mice. (PubMed, J Nutr Biochem) - "The inhibition of PR on LPS-induced inflammatory response were reversed by AMPK inhibitor compound C and SIRT1 inhibitor EX-527. In conclusion, the data demonstrated that PR exhibited therapeutic effects against LPS-induced endometritis through attenuating ferroptosis and inflammatory response."

Journal • Preclinical • Endometriosis • Infertility • Inflammation • Sexual Disorders • GPX4 • TNFA

Ponicidin attenuates Aβ1-42-induced hippocampal cell injury through SIRT1 and PI3K/Akt pathways. (PubMed, Mol Biol Rep) - "These findings suggest that ponicidin exerts neuroprotective effects against Aβ1-42-induced hippocampal injury by enhancing SIRT1 and activating PI3K/Akt signaling, highlighting its potential as a therapeutic candidate for AD."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Schisandrin B regulates the SIRT1/PI3K/Akt signaling pathway to ameliorate Ang II-infused cardiac fibrosis. (PubMed, Iran J Basic Med Sci) - "SchB increased SIRT1 expression while decreasing TGF-β1, α-SMA, collagen I, and collagen III, whereas EX-527, an inhibitor of SIRT1, recovered their activities in vitro. Furthermore, SchB elevated SIRT1 expression while lowering the expressions of p-PI3K (p85, Tyr458) and p-Akt (Ser473) proteins. Our results suggest that SchB regulates the SIRT1/PI3K/Akt pathway to prevent Ang II-infused cardiac fibrosis."

Journal • Cardiovascular • Fibrosis • Heart Failure • Immunology • CTGF • TGFB1

Trigonelline attenuated sepsis-induced acute kidney injury by activating NAD+/SIRT1 Pathway. (PubMed, Physiol Res) - "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."

Journal • Acute Kidney Injury • Infectious Disease • Nephrology • Oncology • Renal Disease • Septic Shock • IL1B • NOX4 • TNFA

Puerarin attenuates S. aureus-induced mastitis through inhibiting inflammation and ferroptosis by activating the SIRT1/p53/SLC7A11 signaling pathway. (PubMed, Microbiol Spectr) - "In vitro, the inhibitory effects of puerarin on S. aureus-induced inflammation and ferroptosis were prevented by the SIRT1 inhibitor EX-527...Puerarin is the main isoflavonoid active ingredient in Pueraria lobata and has a wide range of pharmacological effects. We found that it could attenuate mastitis induced by Staphylococcus aureus."

Journal • Hepatology • Infectious Disease • Inflammation • Liver Failure • GPX4 • IL1B • MPO • SLC7A11 • TNFA

Erythropoietin (EPO) Alleviates Chronic Stress-Induced Depression by Modulating SIRT1-Mediated Mitochondrial Function. (PubMed, J Neuroimmune Pharmacol) - "EX-527 exposure significantly increased Ac-LC3B precipitation in the hippocampus of CRS + EPO-treated mice and the COXIV/LAMP1 ratio in the HT22 cells. In summary, these results suggested that EPO antidepressant effects were mediated through SIRT1 regulation, which influenced LC3B deacetylation, improving CRS-induced mitochondrial dysfunction and autophagy impairment."

Journal • CNS Disorders • Depression • Mental Retardation • Metabolic Disorders • Mood Disorders • Psychiatry • ATG5 • FOXO1 • LAMP1 • NAMPT • SIRT1 • STAT5

Mechanism of salidroside in inhibiting expression of adhesion molecules in oxLDL-induced endothelial cells by regulating ferroptosis mediated by SIRT1/Nrf2 (PubMed, Zhongguo Zhong Yao Za Zhi) - "The intervention effect of high concentration SAL was the most significant. ML385 and EX527 could partially offset the protection of SAL on mitochondrial structure and MMP and reverse the ability of SAL to up-regulate the expression of SIRT1,Nrf2,SLC7A11,GPX4,FPN1, and FTH1 and down-regulate the expression of ICAM-1 and VCAM-1(P<0.05 or P<0.01).To sum up, SAL could reduce the expression of ICAM-1 and VCAM-1 in oxLDL-induced endothelial cell, which may relate to activation of SLC7A11/GPX4 antioxidant signaling pathway mediated by SITR1/Nrf2, up-regulation of FPN1 and FTH1 expression, and inhibition of ferroptosis."

Journal • Dyslipidemia • FTH1 • GPX4 • ICAM1 • SIRT1 • SLC7A11 • TERC • VCAM1

Influence of rutin on LPS-induced inflammation, oxidative stress, and autophagy in bovine mammary epithelial cells. (PubMed, J Dairy Sci) - "The mechanism of the protective effect of rutin on BMEC was investigated using the SIRT1 specific inhibitor EX-527...This study confirms that rutin reduces LPS-induced inflammation, autophagy, and oxidative stress in BMEC through the SIRT1/NLRP3 pathway. These findings provide new insights into addressing mastitis in dairy cows and offer promising clinical applications for future therapeutic interventions."

Journal • Inflammation • BECN1 • CAT • NLRP3

ARA290 Attenuates Apical Periodontitis via SIRT1/NF-κB/IL-1β Pathway Modulation. (PubMed, Int Dent J) - "ARA290 plays a protective role by modulating the SIRT1/NF-κB/IL-1β signalling pathway in apical periodontitis, which may provide a new direction for the adjuvant treatment of apical periodontitis."

Journal • Dental Disorders • Inflammation • Osteoporosis • Periodontitis • IL1B • TRAP

Apigenin attenuates myocardial ischemia-reperfusion injury through miR-448/SIRT1 axis. (PubMed, Iran J Basic Med Sci) - "Compared to the OGD/R+API group, the above indicators were significantly reversed in the OGD/R+API+miR-448 mimic group, OGD/R+API+EX527 group, and OGD/R+API+CA-5f (autophagy inhibitor) group. API regulates autophagy and apoptosis via the miR-448/SIRT1 axis against MIRI."

IO biomarker • Journal • Cardiovascular • Myocardial Ischemia • Reperfusion Injury • BAX • BCL2 • CASP3

L-Tryptophan Produced by Bifidobacterium pseudocatenulatum NCU-08 Delays Aging in SAMP8 Mice by Activating the Sirt1/P53/P21/Rb Signaling Pathway. (PubMed, Aging Cell) - "Interestingly, this antiaging effect was inhibited after the intervention of the Sirt1 inhibitor EX-527. This study is the first to confirm the antiaging properties of NCU-08 isolated from the fecal samples of seven centenarians in Jiangxi Province, providing data support for the future development of probiotic preparations with antiaging effects."

Journal • Preclinical • CDKN1A

Soyasapogenol B prevents sarcopenia by increasing skeletal muscle mass and function through the Sirt1/PGC-1α and PI3K pathway. (PubMed, Biomed Pharmacother) - "The upregulation of mitochondrial biogenesis and myogenic differentiation by soyasapogenol B was attenuated by treatment with EX-527, a SIRT1 inhibitor, and LY294002, a PI3K inhibitor. In conclusion, soyasapogenol B increased skeletal muscle mass, skeletal muscle strength and endurance by activating the Sirt1 and PI3K pathways. Thus, by promoting protein synthesis and mitochondrial biogenesis, soyasapogenol B could be a potential prevention option for sarcopenia."

Journal • Genetic Disorders • Obesity • Oncology • Sarcopenia

Gpbar1-mediated SIRT1-PGC-1α axis maintains mitochondrial homeostasis and mitigates renal injury in obstructive jaundice. (PubMed, Sci Rep) - "After treatment with the SIRT1 inhibitor EX527, PGC-1α expression significantly decreased. We used SIRT1 inhibitors, activators and PGC-1α inhibitors to conduct positive and negative regulation experiments and confirmed the hierarchical regulatory effect of Gpbar1 on SIRT1-PGC-1α. Gpbar1 influences oxidative stress resistance via the SIRT1-PGC-1α axis, promotes mitochondrial functional homeostasis, and alleviates kidney injury induced by obstructive jaundice."

Journal • Metabolic Disorders • Renal Disease

Exendin-4 alleviates diabetic retinopathy by activating autophagy via regulation of the adenosine monophosphate-activated protein kinase/sirtuin 1 pathway. (PubMed, J Mol Histol) - "Additionally, twenty Sprague Dawley rats were divided into control, DR, Exendin-4, and Exendin-4 + ex-527 groups. However, SIRT1 inhibitor reversed the therapeutic effects of Exendin-4. Our results suggest that the efficacy of Exendin-4 in the treatment of DR is achieved by activating autophagy; this therapeutic mechanism may involve regulation of the AMPK/SIRT1 pathway."

Journal • Diabetes • Diabetic Retinopathy • Inflammation • Ophthalmology • Retinal Disorders

THE MECHANISM OF PARP INHIBITOR ENHANCE DECITABINE FUNCTION IN TET2-DEFICIENT MYELOID LEUKEMIA (EHA 2025) - "EX527 reduced the expression of PARP, SIRT1, γ-H2AX, and XRCC1 proteins, as well as SIRT1.The construction of the shTET2 HL60 and K562 stable-transformed cell lines was effective, and compared to the control group, the expression of DNA damage repair proteins including PARP1 and -HA2X was up-regulated. Due to the functional lack of TET2/SIRT1, after decitabine therapy of TET2-deficient myeloid tumors, the DNA repair mechanism in cancer cells activated DNA repair enzymes such PARP1 and XRCC1 instead. Decitabine's pro-apoptotic activity on shTET2 HL60 and K562 cells was therefore increased by PARP inhibitors, which synergistically increased the tumor-killing effect."

Hematological Malignancies • Leukemia • Oncology • CASP3 • H2AX • SIRT1 • TET2 • XRCC1

Multitargeted Biological Actions of Polydatin in Preventing Pseudogout Acute Attack (EULAR 2025) - "Animals were randomised to receive PD or colchicine (control drug) according to a prophylactic protocol...Anakinra and J-113863 were used to assess their anti-inflammatory effect, while EX527 served to evaluate the effect of PD on SIRT-1... PD effectively prevents acute inflammatory responses to CPP crystals in mice, preserving both articular and muscular structures. Its anti-inflammatory effects are primarily mediated through pathways regulating leukocyte migration and the suppression of pro-inflammatory mediator."

Musculoskeletal Diseases • Rheumatology • CCL23 • CXCL8 • IL18 • IL1B • IL6 • TNFA

Alpha-asarone relieves nasal inflammation, epithelial barrier damage, and mitochondrial damage in allergic rhinitis by inhibiting mitochondrial ROS via the SIRT1/PGC-1α pathway. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Using a SIRT1 inhibitor (EX527) and a PGC-1α activator (ZLN005), it was demonstrated that ASA upregulates SIRT1 to promote PGC-1α deacetylation, thereby suppressing mtROS, restoring mitochondrial function, and alleviating nasal inflammation and epithelial barrier damage...These results indicate that ASA mitigates nasal inflammation and epithelial barrier damage in AR by suppressing mtROS via the SIRT1/PGC-1α pathway. As a natural agent, ASA presents a promising AR treatment alternative with potentially fewer side effects than conventional therapies."

Journal • Allergic Rhinitis • Immunology • Inflammation • Mucositis • IL13 • IL4

FOXQ1 Suppressing Apoptosis in Colorectal Cancer Cells by P53 Deacetylation. (PubMed, J Coll Physicians Surg Pak) - "FOXQ1 promotes chemoresistance in CRC by upregulating SIRT1 expression and promoting P53 deacetylation, thereby inhibiting apoptosis triggered by DDR."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Ginsenoside Rg1 Downregulates miR-9-5p Expression to Modulate SIRT1-Mediated Mitochondrial Dysfunction and Ameliorate Alzheimer's Disease. (PubMed, Mol Neurobiol) - "Ginsenoside Rg1 treatment in AD mice reduced miR-9-5p expression, increased SIRT1 level, attenuated mitochondrial dysfunction, and effectively improved AD symptoms in mice, while such effect can be either reversed by miR-9-5p agomir or SIRT1 inhibitor (EX527)...Inhibition of mitochondrial autophagy partially reversed the ameliorative effect of ginsenoside Rg1 on mitochondrial dysfunction and cellular damage in HT-22 cells. Ginsenoside Rg1 down-regulates miR-9-5p expression to modulate SIRT1-mediated mitochondrial dysfunction, hereby attenuating Aβ1-42 induced cell injury in HT-22 cells and alleviating AD in mice."

Journal • Alzheimer's Disease • CNS Disorders • Metabolic Disorders • BECN1 • SIRT1

Vitexin alleviates cerebral ischemia/reperfusion injury by regulating mitophagy via the SIRT1/PINK1/Parkin pathway. (PubMed, Brain Res Bull) - "Vitexin ameliorates CIRI by activating mitophagy via the SIRT1/PINK1/Parkin pathway."

IO biomarker • Journal • B Cell Lymphoma • Cardiovascular • CNS Disorders • Lymphoma • Oncology • Reperfusion Injury • BAX • MAP1A • PTEN • SQSTM1

Marein from Coreopsis tinctoria Nutt. alleviates oxidative stress and lipid accumulation via SIRT1/Nrf2 signaling. (PubMed, Sci Rep) - "Mechanistically, Marein activated the Sirtuin-1 (SIRT1)/Nuclear factor-erythroid-2-related factor 2 (Nrf2) signaling, which was confirmed by the reversal of its protective effects upon treatment with EX-527 (a specific SIRT1 inhibitor). These findings suggested that Marein exerted its antioxidative and lipid-lowering effects via the SIRT1/Nrf2 signaling, highlighting its potential as a therapeutic candidate for hyperlipidemia and related metabolic disorders."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • LDLR