SRT1720 / GSK - LARVOL DELTA

Single-cell transcriptomics and multi-omics integration identify necroptosis-driven core targets and tubular-immune crosstalk in chronic kidney disease. (PubMed, Comput Biol Chem) - "Multi-omics profiling showed that DHFZ confers nephroprotection by restoring SIRT1-mediated suppression of necroptosis in VCAM1+ PT cells and disrupting maladaptive THBS1-CD47 tubular-macrophage crosstalk. These findings identify SIRT1 as a tractable therapeutic target in CKD."

Journal • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • RIPK1 • SIRT1 • TP53 • VCAM1

Adenoviral-Mediated SIRT1 Expression Restores Lung Architecture and Reduces Fibrotic Progression in Experimental Models. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "Pharmacological modulation of SIRT1 was also tested using the activator SRT1720 and the inhibitor EX527. Adenoviral SIRT1 gene delivery exerts protective effects on the alveolar epithelium in vitro and reverses established PF in vivo through epigenetic regulation of key profibrotic pathways. This dual approach highlights the translational potential of SIRT1 as a therapeutic target for PF."

Journal • Fibrosis • Gene Therapies • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • SIRT1

Syringaresinol activates the skeletal muscle SIRT1-FNDC5/irisin axis to enhance weight management. (PubMed, 3 Biotech) - "Differentiated C2C12 myotubes were treated with SYR, the SIRT1 activator SRT1720, and the SIRT1 inhibitor EX-527 to assess Irisin-related readouts, mitochondrial-associated markers, gene expression, and SIRT1/PGC-1α protein abundance. SYR is associated with SIRT1/PGC-1α-related remodeling, Irisin-related readouts, and attenuated HFD-induced weight gain. These findings support SYR as a candidate nutritional modulator of muscle-adipose metabolic communication, while causal in vivo mediation by SIRT1, FNDC5, or Irisin requires further pathway-specific validation."

Journal • PPARG

Pharmacological activation of SIRT1 alleviates sepsis-associated acute kidney injury by improving renal mitochondrial energy metabolism. (PubMed, Ren Fail) - "SRT1720 ameliorated renal pathological injury and mitochondrial-related abnormalities, whereas EX-527 worsened these changes. These findings suggest that SIRT1 activation attenuates SA-AKI, at least partly by maintaining renal mitochondrial energy homeostasis."

Journal • Acute Kidney Injury • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Septic Shock • SIRT1

Mitochondrial proteomic signatures of postcardiac arrest brain injury reveal potential therapeutic targets. (PubMed, J Pharmacol Exp Ther) - "Treatment with the silent information regulator 1 activator SRT1720 was associated with the reversal of these proteomic alterations, selective restoration of complex I activity, and recovery of mitochondrial calcium regulation, thereby re-establishing energy metabolism and metabolic homeostasis. These integrated, multilevel findings provide a mechanistic framework for targeting mitochondrial dysfunction in postcardiac arrest brain injury and support SRT1720 as a promising therapeutic candidate."

Journal • Cardiovascular • CNS Disorders • Metabolic Disorders • Vascular Neurology • NDUFB1

SIRT1/PGC-1α Axis and CPT1A-Mediated Metabolic Reprogramming Reshape Macrophage Polarization to Ameliorate Intervertebral Disc Degeneration. (PubMed, Pharmacol Res) - "In vivo administration of the SIRT1 agonist SRT1720 or CPT1A agonist C75 alleviated IDD progression. This study indicates that the SIRT1/PGC-1α/CPT1A axis regulates macrophage polarization through metabolic reprogramming and provides potential therapeutic targets for IDD."

Journal • Back Pain • Lumbar Back Pain • Musculoskeletal Pain • Pain • CPT1A

SIRT1 deacetylates GAPDH to drive microglial glycolysis and neuroinflammation. (PubMed, Front Immunol) - "Pharmacological activation of SIRT1 (SRT1720) reversed this modification and enhanced glycolytic output, mimicking the effects of the deacetylation-mimetic K254R mutant. Glycolytic inhibition with 2-deoxyglucose reduced most of the excess cytokines, confirming enhanced flux as the causal factor in K254-driven inflammatory amplification. Thus, SIRT1-GAPDH signaling represents a post-translational axis linking sirtuin activity directly to glycolytic enzyme function, distinct from SIRT1's traditional transcriptional roles and serving as a viable molecular checkpoint in microglial immunometabolism."

Journal • Inflammation • GAPDH • IFNG • IL1B • IL6 • SIRT1 • TNFA

SIRT1 Activation Ameliorates Neuroinflammation and Cognitive Impairment in a Murine SAE Model and is Associated with the Nrf2/GPX4 Pathway. (PubMed, Neurochem Res) - "This study investigates the neuroprotective potential of selective Sirtuin 1 (SIRT1) activation using the synthetic agonist SRT1720 in a male C57BL/6 J murine model of SAE...Concurrently, it attenuated neuroinflammation by suppressing microglial activation and NLRP3 inflammasome activity, thereby decreasing the maturation of proinflammatory cytokines. These findings suggest SIRT1 activation coordinately counteracts both ferroptotic and inflammatory damage in SAE, presenting a compelling therapeutic strategy."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Septic Shock • GPX4 • NLRP3

SRT1720-loaded exosome-mimetic nanovesicles promote mitophagy via SIRT1/PARKIN activation to ameliorate diabetic cerebral infarction in a preclinical rat model. (PubMed, Int J Pharm ) - "In the DCI model, SRT1720@M improved neurological deficits, reduced infarct volume, and alleviated behavioral disorders by inhibiting apoptosis and inflammation and promoting mitophagy and mitochondrial function through activation of the SIRT1/PARKIN pathway. SRT1720@M alleviates DCI by activating the SIRT1/PARKIN pathway and promoting mitophagy, highlighting its potential as a promising preclinical therapeutic strategy."

Journal • Preclinical • Behavior Disorders • CNS Disorders • Diabetes • Inflammation • Mental Retardation • Metabolic Disorders • Psychiatry • IL1B • SIRT1 • TNFA

Assessing SIRT1 dual-activity compounds for preventing osteoarthritis (ACS-Fall 2026) - "A. Comparison of SIRT1 Activation ability between 10mM SRT1720 positive control and all 23 Compounds (10mM), using human recombinant purified Sirt1 and Cathepsin B. Compounds whose RFU is within the green area are selected for further analysis."

Immunology • Osteoarthritis • Rheumatology • CTSB • SIRT1

Sirtuin signalling governs calcium homeostasis and mitochondrial function in metabolic syndrome cardiomyocytes. (PubMed, Exp Physiol) - "MetS cardiomyocytes exhibited mitochondrial depolarization, increased reactive oxygen species production, elevated basal cytosolic Ca2+ levels, reduced Ca2+ transient amplitude and decreased sarcoplasmic reticulum Ca2+ content. Notably, pharmacological inhibition of SIRT1 with EX527 in control cardiomyocytes recapitulated key features of the MetS phenotype, whereas SIRT1 activation with SRT1720 restored mitochondrial membrane potential, reduced reactive oxygen species production, improved Ca2+ handling, normalized aberrant phosphorylation of Ca2+-handling proteins and attenuated apoptotic signalling. Collectively, these findings identify SIRT1 as a critical integrator of mitochondrial function and Ca2+ homeostasis during metabolic stress, highlighting sirtuin-dependent pathways as promising therapeutic targets in metabolic cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Metabolic Disorders

Sodium Danshensu alleviates oxidative stress-induced endothelial apoptosis and senescence by modulating the SIRT1/p53 pathway. (PubMed, J Ethnopharmacol) - "SDSS alleviates oxidative stress-induced vascular injury and endothelial dysfunction, and that these protective effects are associated with activation of the SIRT1/p53 pathway. These results offer preliminary correlative evidence supporting the traditional use of Danshen in cardiovascular protection, and suggest that SDSS warrants further investigation as a candidate for oxidative stress-associated vascular dysfunction."

IO biomarker • Journal • Cardiovascular • BCL2 • CDKN1A

Pharmacological Modulation of ALDH2-SIRT1-Endoplasmic Reticulum Stress Axis in MNU-Induced Retinal Degeneration in C57BL/6 Mice: An In Vivo Study. (PubMed, J Vis Exp) - "Pharmacological inhibition of SIRT1 (via EX-527) diminished the protective effects of Alda-1, and ERS induction (via TUN) nearly abolished its benefits. Conversely, SIRT1 activation (via SRT1720) mitigated the adverse effects of Daidzin, while ERS inhibition (via 4-PBA) partially alleviated Daidzin's impact...Besides, pharmacological modulation of the SIRT1/ERS pathways intervened in the regulatory effects of Alda-1 and Daidzin on the aldehyde metabolism. Overall, ALDH2 activation protected retinal structure and regulated aldehyde metabolism, highlighting the critical role of the ALDH2-SIRT1/ERS signaling axis in mitigating retinal degeneration."

Journal • Preclinical • Ophthalmology • ALDH2 • SIRT1

VEGF inhibitor-induced vascular dysfunction involves redox-sensitive PARP activation and SIRT1 disruption. (PubMed, Exp Physiol) - "Molecular studies were performed in axitinib (VEGFR inhibitor)-treated human aortic endothelial cells, and vascular studies were undertaken in isolated intact vessels from mice...This was accompanied by increased p53 acetylation; these effects were mitigated by olaparib or the SIRT1 activator SRT1720...In conclusion, inhibition of VEGFR signalling induces oxidative stress and PARP activation, leading to SIRT1 downregulation, endothelial dysfunction and vascular inflammation. Targeting PARP activation or enhancing SIRT1 activity might represent promising strategies to mitigate VEGF inhibitor-induced vascular complications."

Journal • Cardiovascular • Hypertension • Inflammation • Oncology • EDN1 • ICAM1 • IL6 • SIRT1 • VCAM1

The protective role of SIRT1 in cardiovascular disease: from molecular mechanisms to potential therapeutic strategies. (PubMed, Expert Opin Ther Targets) - "It examines the preclinical efficacy of SIRT1 activators, such as resveratrol and SRT1720, and discusses challenges including dose dependency, specificity, and barriers to clinical translation...We believe that developing highly specific SIRT1 activators, identifying predictive biomarkers, and elucidating tissue-selective regulatory mechanisms can amplify SIRT1's protective effects in cardiac diseases. Current and future clinical trials should establish the safety and efficacy of SIRT1-targeted therapies at the earliest possible stage."

Journal • Review • Atherosclerosis • Cardiovascular • Heart Failure • Inflammation • SIRT1 • SIRT7

Embryo developmental and morphokinetic patterns in the domestic cat (Felis catus): associations with maternal age and SRT1720 supplementation during oocyte in vitro maturation. (PubMed, Theriogenology) - "Morphokinetic monitoring provided descriptive observations suggesting distinct age-related developmental profiles. These findings provide baseline information on feline developmental kinetics and may support further investigation of metabolic modulators in feline assisted reproduction."

Journal • Preclinical • Gynecology • Metabolic Disorders

Activation of Sirt1 by Glyasperin F Suppresses PI3K/Akt/HIF-1α Signaling and Inhibits Glycolytic Metabolism to Ameliorate Pathology in Rheumatoid Arthritis-Associated Interstitial Lung Disease. (PubMed, FASEB J) - "This model was combined with pharmacological modulation of Sirt1 using EX527 and SRT1720, as well as HIF-1α overexpression or empty-vector lentiviral transduction, to dissect the underlying molecular mechanisms. HIF-1α overexpression reversed these therapeutic effects. This study suggests that Glyasperin F has the potential to serve as a natural candidate compound for the regulation of glycolytic metabolism in the intervention of RA-ILD."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • HIF1A • IL1B • LDHA • PKM • SIRT1 • TGFB1

SIRT1 in Cardiac Diseases: Molecular Mechanisms, Therapeutic Potential, and Future Directions. (PubMed, Int J Mol Sci) - "Preclinical studies demonstrate that natural compounds (resveratrol, quercetin, curcumin, ginsenosides, tanshinone IIA, bergenin, swietenine) and synthetic SIRT1 activators (SRT1720, anilinopyridine derivatives) attenuate cardiac injury and improve function...Challenges remain in achieving cardiac-specific targeting, optimizing NAD+ availability, and translating preclinical findings into clinical practice. Future research should integrate multi-omics approaches, single-cell transcriptomics, and precision medicine strategies to unlock the therapeutic potential of SIRT1 in cardiac diseases."

Journal • Review • Atherosclerosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Myocardial Ischemia • Reperfusion Injury • Sleep Disorder • GPX4 • SIRT1

Protective Role of SIRT1 Activation Against Retinal Injury Caused by Polystyrene Micro/Nanoplastics Exposure. (PubMed, Environ Pollut) - "In conclusion, PS-MPs or PS-NPs promote oxidative stress and senescence in RPE cells and retinal tissue via downregulation of SIRT1 and antioxidant defenses, while SRT1720 provides protective effects. These findings SIRT1 as a potential therapeutic target for plastic-induced retinal injury."

Journal • SIRT1 • SOD2

Salvianolic Acid B Ameliorates Metabolic-associated Steatohepatitis in Mice by Inhibiting Hepatocyte Ferroptosis via Regulation of the SIRT1/p53 Axis. (PubMed, Free Radic Biol Med) - "Sal B ameliorates MASH in mice via directly regulating SIRT1/p53 signaling to suppress hepatocyte ferroptosis. Targeting hepatocyte ferroptosis through SIRT1 activation is a promising therapeutic strategy for MASH."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis

SIRT1 protects against UVA-induced photoaging by suppressing oxidative stress and FOXO3a acetylation in human dermal fibroblasts. (PubMed, J Photochem Photobiol B) - "We found that pharmacological activation of SIRT1 with SRT1720 significantly mitigated UVA-induced damage, reducing oxidative stress, DNA damage (8-OHdG), cellular senescence, and extracellular matrix degradation...Crucially, all protective effects of SIRT1 activation were completely abolished upon FOXO3a knockdown, genetically establishing FOXO3a as the essential downstream effector. Our results delineate the SIRT1-FOXO3a deacetylation axis as a central regulatory pathway that coordinates antioxidant defense and ECM homeostasis, highlighting its potential as a precise therapeutic target for mitigating skin photoaging."

Journal • FOXO3 • SIRT1 • SOD2

The Host NADase CD38 Promotes JEV Replication by Targeting the NAD+/SIRT1 Axis. (PubMed, Microorganisms) - "The dominance of this metabolic axis was confirmed through bidirectional pharmacological interventions; while SIRT1 inhibition using EX527 restored JEV replication, SIRT1 activation using SRT1720 suppressed it in wild-type cells. Our work reveals that JEV hijacks the CD38-NAD+-SIRT1-p53 axis to overcome host metabolic defenses in reproductive cell models, establishing CD38 as a promising therapeutic target."

Journal • CNS Disorders • Infectious Disease • CD38

Uremic toxin p‑cresyl sulfate enhances the calcification of aortic valvular interstitial cells via klotho/sirtuin‑1 signaling. (PubMed, Mol Med Rep) - "The present study demonstrated that PCS induced VIC calcification by activating HIF‑1α signaling and downregulating klotho. Treatment with klotho or SRT1720 was shown to attenuate PCS‑mediated activation of the NF‑κB/RUNX2 signaling pathway, suggesting that these agents demonstrate notable therapeutic potential for targeting PCS‑induced CAVD."

Journal • Cardiovascular • Chronic Kidney Disease • Heart Failure • Inflammation • Nephrology • Renal Disease • HIF1A • KL • RUNX2 • SIRT1

SIRT1 Prevents Ferroptosis in Corneal Epithelial Cells by Enhancing HIF1α Protein Stability in Dry Eye Disease. (PubMed, Adv Sci (Weinh)) - "Pharmacological activation of SIRT1 using SRT1720 alleviated oxidative damage and suppressed ferroptosis in corneal epithelial cells both in vitro and in vivo...The SIRT1-HIF1α axis positively regulates GPX4 levels, thereby inhibiting ferroptosis activation. These results reveal a previously unrecognized pathway of ferroptosis regulation in DED and suggest a potential therapeutic strategy for reducing oxidative damage in corneal epithelium."

Journal • Corneal Abrasion • Dry Eye Disease • Ophthalmology • Targeted Protein Degradation • GPX4 • HIF1A • SIRT1

SIRT1 agonist SRT1720 alleviates cerebral ischemia-reperfusion injury by inhibiting lactate-mediated SOD2 Lactylation and suppressing NCOA4-mediated ferritinophagy-ferroptosis. (PubMed, Cell Signal) - "Importantly, treatment with the SIRT1 agonist SRT1720 effectively inhibited SOD2 lactylation, restored its antioxidant activity, suppressed ferritinophagy and ferroptosis, and attenuated microglial injury. These findings identify the SOD2-K114la/NCOA4 axis as a critical mediator of CIRI progression and suggest that SIRT1 activation may represent a potential therapeutic strategy for mitigating lactylation-dependent ischemic injury."

Journal • Cardiovascular • CNS Disorders • Metabolic Disorders • Reperfusion Injury • Vascular Neurology • NCOA4 • SIRT1 • SOD2