SRT1720 / GSK - LARVOL DELTA

Defective mitophagy of CD4+T cells in ITP via NAD+/SIRT1 reduction (ASH 2025) - "Nicotinamide riboside (NR) and a SIRT1 agonist (SRT1720) were administered to ITPCD4+ T cells in vitro to reveal the role of the NAD+/SIRT1 axis in mitophagy deficiency. GSEA revealed that the expression oftype I interferon in ITP CD4+ T cells and the pathways positively regulated by type 1 interferon weresignificantly upregulated, suggesting that mitophagy deficiency may promote the production of type Iinterferons by CD4+ T cells in ITP, thereby participating in the immune imbalance in ITP.ConclusionDefects in the NAD+/SIRT1 axis lead to mitophagy deficiency in ITP CD4+ T cells, resulting in an immuneimbalance in ITP. Targeted correction of the NAD+/SIRT1 axis can regulate CD4+ T-cell differentiationthrough the correction of mitophagy in ITP CD4+ T cells, providing new therapeutic ideas and targets forthe clinical treatment of ITP."

Genetic Disorders • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Inflammation • Metabolic Disorders • Thrombocytopenia • Thrombocytopenic Purpura • BST1 • CD4 • PINK1 • SIRT1

AMPK/SIRT1/PGC-1α Signaling Pathway: Molecular Mechanisms and Targeted Strategies From Energy Homeostasis Regulation to Disease Therapy. (PubMed, CNS Neurosci Ther) - "The AMPK/SIRT1/PGC-1α pathway represents a cornerstone target at the intersection of metabolism, aging, and disease. Current therapeutic strategies-including pharmacological activators (e.g., metformin, SRT1720), natural compounds (e.g., resveratrol), lifestyle interventions (e.g., exercise, caloric restriction), and emerging technologies (e.g., gene editing, exosomal miRNAs)-offer multidimensional avenues for intervention. Future research must prioritize elucidating tissue-specific regulatory mechanisms, such as AMPK isoform diversity and PGC-1α interactome dynamics, to enable precision therapeutics and successful clinical translation for a range of complex disorders."

Journal • Review • Alzheimer's Disease • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Diabetes • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Movement Disorders • Nephrology • Parkinson's Disease • Pulmonary Disease • Renal Disease • Respiratory Diseases • NLRP3 • SLC2A4 • SMAD3 • TGFB1

Thyroid hormone deficiency worsens outcomes in vaccinia virus infection. (PubMed, J Virol) - "Further highlighting the link between thyroid hormones and immune defense, we show that SRT1720, a Sirtuin 1 activator, reduces thyroid hormone levels and also worsens vaccinia infection when administered to euthyroid mice...Hypothyroidism also impairs the amplification of splenic lymphocytes, which play a key role in defense against viral infection. Furthermore, vaccinia virus infection reduces thyroid hormone levels in euthyroid mice, a phenomenon named "non-thyroidal illness syndrome" that often occurs in septic patients, suggesting that, in the context of viral pulmonary infections, thyroid hormone replacement might be a useful therapeutic option."

Journal • Endocrine Disorders • Infectious Disease • Respiratory Diseases • Septic Shock • SIRT1

Ginsenoside Rb1 Alleviates Asthma Inflammation by Regulating Mitochondrial Dysfunction through SIRT1/PGC-1α and PI3K/AKT Pathways. (PubMed, Biol Pharm Bull) - "In BEAS-2B cells, Rb1 plays a role similar to that of a SIRT1 agonist (SRT1720), including enhancing mitochondrial membrane potential and decreasing mitochondrial ROS and DRP1 translocation to mitochondria. Our findings suggest that Rb1 maintains mitochondrial integrity by activating SIRT1/PGC-1α and inhibiting PI3K/AKT, thereby ameliorating asthmatic airway inflammation."

Journal • Asthma • Immunology • Inflammation • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • CAT

Swietenine alleviated cardiomyocyte inflammation in diabetic cardiomyopathy by regulating NAMPT/SIRT1. (PubMed, Int Immunopharmacol) - "In vitro siRNA-mediated NAMPT knockdown abolished swietenines anti-inflammatory effects, while SIRT1 activation with SRT1720 restored its NLRP3 inhibitory capacity. Collectively, these findings indicate that swietenine ameliorates DCM via the NAMPT/SIRT1 pathway-mediated suppression of NLRP3 inflammasome activation, highlighting its potential as a therapeutic agent for DCM."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Fibrosis • Immunology • Inflammation • IL18 • IL1B • NAMPT • NLRP3 • SIRT1

SIRT1 inhibits ferroptosis of granulosa cells in polycystic ovarian syndrome. (PubMed, Int J Biol Macromol) - "Functional assays revealed that SIRT1 overexpression or pharmacological activation by SRT1720 significantly decreased lipid peroxidation and reactive oxygen species levels, thereby alleviating ferroptosis (p < 0.05). Mechanistically, co-immunoprecipitation indicated that SIRT1 interacted with Nrf2, and molecular docking suggested potential SIRT1-binding compounds. Collectively, these findings indicate that SIRT1 suppresses ferroptosis in granulosa cells via Nrf2 deacetylation, providing new insight into PCOS pathogenesis and suggesting SIRT1 as a potential therapeutic target."

Journal • Endocrine Disorders • Polycystic Ovary Syndrome • SIRT1

Targeting Deacetylase Sirt-1 Reprograms Treg Function in Immune Thrombocytopenia (ASH 2024) - "Furthermore, EX527, a Sirt-1 inhibitor and SRT1720, a Sirt-1 agonist, as well as lentiviral interference of Sirt-1 in Tregs were used to verify the target of anti-CD38 therapy. In both Group B and C, significantly ameliorated thrombocytopenia, increasedproportion of splenic Tregs, down-regulated Sirt-1 in Foxp3 positive frozen sections, and restoration of anti-/pro-inflammatory cytokine profiles was demonstrated, compared with Group A. Conclusion : In summary, CD38 monoclonal antibody potentially reprograms the immunosuppressive function of Tregs by inhibiting Sirt-1, which provides a novel target for the management of ITP. This study suggested versatile mechanisms of anti-CD38 therapy in autoimmune disorders and rationalized its long-term efficacy in patients with ITP."

IO biomarker • Graft versus Host Disease • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Thrombocytopenia • Thrombocytopenic Purpura • CD4 • CD8 • FOXP3 • IL2RA • ITGB3 • SIRT1

Meiotic cohesion requires Sirt1 and preserving its activity in aging oocytes reduces missegregation. (PubMed, EMBO Rep) - "Strikingly, age-dependent segregation errors are significantly reduced if mothers are fed SRT1720 while their oocytes age. Our data suggest that maintaining Sirt1 activity in aging oocytes may provide a viable therapeutic strategy to decrease age-dependent segregation errors."

Journal • SIRT1

The Sirt1 Activator SRT1720 Mitigates Human Monocyte Activation and Improves Outcome During Gram-Negative Pneumosepsis in Mice. (PubMed, Int J Mol Sci) - "Plasma IL-6 and TNF-α were significantly lower in SRT1720-treated mice at 42 h. Finally, while SRT1720 did not impact bacterial loads in the lungs, it reduced bacterial burden in blood, with a similar trend observed in liver homogenates. In conclusion, the Sirt1 activator SRT1720 exerts anti-inflammatory effects on human monocytes, reduces local and systemic inflammation and organ injury, and diminishes bacterial dissemination in murine pneumosepsis."

Journal • Preclinical • Infectious Disease • Inflammation • Pneumonia • Respiratory Diseases • GLI2 • IL6 • TNFA

The Role of Hepatic SIRT1: From Metabolic Regulation to Immune Modulation and Multi-target Therapeutic Strategies. (PubMed, J Clin Transl Hepatol) - "Recent studies indicate that natural compounds (e.g., resveratrol, curcumin) improve gut-liver barrier function through microbiota-SIRT1 interactions, while synthetic activators (SRT1720) and NAD+ precursors (NMN) enhance hepatocyte antioxidant capacity and fatty acid β-oxidation. This innovative analysis highlights the spatiotemporal specificity of various SIRT1 activators, emphasizing that tissue-selective delivery and dynamic dosage optimization are crucial for overcoming clinical translation challenges. By integrating mechanistic and translational insights, this review provides a novel foundation for precision intervention strategies targeting SIRT1 network reprogramming."

Journal • Review • Hepatology • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • SIRT1

Sirt1 ameliorated cardiac autophagic flux blockage via Prx2 during myocardial ischemia/reperfusion injury. (PubMed, Biochem Pharmacol) - "Importantly, Sirt1-Prx2-autophagic flux signaling pathway was demonstrated by Sirt1 agonist-SRT1720. These findings identify Sirt1 as a pivotal regulator of autophagic flux and oxidative homeostasis via the Prx2 pathway, offering a novel therapeutic target to mitigate MI/R injury through restoration of autophagy and redox balance."

Journal • Cardiovascular • Myocardial Ischemia • Reperfusion Injury • PRDX2 • PRRX2 • SIRT1

Single-cell transcriptome analysis highlights a critical role of ATG5 for endothelial cells in diabetic nephropathy. (PubMed, Hum Cell) - "However, Atg5 silencing reversed SRT1720-mediated alterations in these parameters. The SIRT1/ATG5 axis-dependent HRGEC autophagy restoration exerts a protective effect on the kidney during DN, offering a scientific ground for developing therapeutic strategies for DN based on autophagy regulation."

Journal • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease • ATG5

Lipin-1 Drives Browning of White Adipocytes via Promotion of Brown Phenotype Markers. (PubMed, Biomedicines) - " Mouse 3T3-L1 preadipocytes were treated during differentiation with either rosiglitazone (RGZ), the SIRT1 activator SRT1720, or the SIRT1 inhibitor EX527. These findings demonstrate that Lipin-1 interacts with the SIRT1-PPARγ-SRSF10 axis in adipocytes and contributes to the acquisition of beige/brown-like characteristics in WAT. This regulatory pathway may represent a potential target for improving lipid metabolism and metabolic health."

Journal • Genetic Disorders • Metabolic Disorders • Obesity • LPIN1 • PPARG • PPARGC1A • PRDM16

Can Sirtuin 1 Serve as a Therapeutic Target in Pulmonary Arterial Hypertension? A Comprehensive Review. (PubMed, Molecules) - "Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, regulates endothelial and vascular smooth muscle function, and its activation by compounds such as resveratrol or SRT1720 shows therapeutic potential by reducing pulmonary and right ventricular pressures and limiting vascular remodeling in both preventive and therapeutic experimental models, highlighting their potential translational relevance. To date, no comprehensive review has focused on the role of SIRT1 in PAH. This review summarizes the molecular mechanisms of SIRT1 action in the cardiopulmonary system and discusses its therapeutic potential in PAH treatment."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • SIRT1

Deacetylase SIRT1 modulates antiviral innate immunity and autoimmune diseases. (PubMed, Int J Biol Macromol) - "Pharmacological inhibition of SIRT1 with EX527 augmented virus-triggered IFN-I responses. In Trex1-deficient mice, a model of autoimmune disease, SIRT1 activation via Resveratrol or SRT1720 ameliorated pathological phenotypes. Collectively, these findings position SIRT1 as a rheostat for innate immune homeostasis through direct deacetylation of IRF3/IRF7, highlighting its therapeutic potential in viral infections, interferonopathies and autoimmune disorders."

Journal • Dermatomyositis • Immunology • Infectious Disease • Inflammatory Arthritis • Interferonopathies • Lupus • Myositis • Sjogren's Syndrome • Systemic Lupus Erythematosus • IFNB1 • IRF7 • TREX1

Hexafluoropropylene Oxide Homologues, the Novel Alternatives to PFOA, Induce Mitochondrial Dysfunction and Cytotoxicity in Leydig Cells through Disrupting SIRT1/PGC-1α Signaling Pathway. (PubMed, Toxicology) - "However, supplementation with the SIRT1 agonist SRT1720 relieved the inhibitory effect of HFPOs on SIRT1/PGC1α signaling pathway and reversed the expression of apoptosis-associated proteins (BAX/BCL2), oxidative stress-associated proteins (SOD1/SOD2), as well as proteins associated with mitochondrial fusion (MFN2/OPA1) and fission (DRP1/FIS1). These results elucidated the involvement of the SIRT1/PGC1α pathway in mediating the cytotoxicity of HFPOs. Notably, the activation of SIRT1 mitigated HFPO-induced toxicity in the TM3 cells, uncovering its potential in safeguarding testicular cells from the damage caused by HFPOs exposure."

IO biomarker • Journal • Metabolic Disorders • BAX • BCL2 • MFN2 • SOD2

Disruption of the SIRT1/PI3K/AKT Signaling Axis Mediates Fluoride-Induced Cardiotoxicity: Evidence from in Vitro and Zebrafish Models. (PubMed, Biol Trace Elem Res) - "Activation of SIRT1 by SRT1720 mitigates these effects, highlighting the protective role of this pathway in F-related cardiac injury. These findings provide mechanistic insights and identify potential molecular targets for the prevention and treatment of fluorosis-associated cardiovascular toxicity."

Journal • Preclinical • Cardiovascular • Inflammation

SIRT1 targeted bioengineered extracellular vesicles chrono-reprogram microglia to reverse non-dipping hypertension - myocardial remodeling and comorbid neuropsychiatric disorders under stress. (PubMed, Int Immunopharmacol) - "SRT1720 attenuated HMGB1 hyperacetylation and reversed non-dipping hypertension...Dual benefits in cardiovascular (myocardial remodeling reversal) and neuropsychiatric (behavioral rescue) domains were consistently observed. Our findings establish CLOCK/Sirt1-mediated microglial activation as a driver of neuroimmune-cardiovascular dysregulation, offering a translational macromolecule platform for chrono-immunotherapy of comorbid disorders."

IO biomarker • Journal • Cardiovascular • CNS Disorders • Fibrosis • Hypertension • Immunology • Inflammation • Mental Retardation • Mood Disorders • Psychiatry • CLOCK • CX3CR1 • HMGB1 • SIRT1

Sirt1 Attenuates Necrotizing Enterocolitis via Hif-1α Deacetylation-Mediated Suppression of Bnip3-Dependent Mitophagy. (PubMed, Free Radic Biol Med) - "Pharmacological Sirt1 activation by SRT1720 effectively attenuated NEC progression through Hif-1α deacetylation and subsequent mitophagy inhibition. Importantly, we provide the first evidence that Sirt1 directly regulates Hif-1α acetylation status in intestinal epithelial cells, establishing a new molecular mechanism linking protein acetylation to mitochondrial quality control in NEC. These findings reveal Sirt1 as a master regulator of intestinal homeostasis and highlight Sirt1 activation as a promising therapeutic approach for NEC treatment."

Journal • Gastrointestinal Disorder • Inflammation • Metabolic Disorders • HIF1A • SIRT1

Circadian Rhythm Cascade SIRT1/PGC-1α/BMAL1 Pathway Regulates Nitroglycerin-Induced Chronic Migraine. (PubMed, Neurochem Res) - "Previous findings have suggested that inflammation activation in the trigeminal nervous system and circadian rhythms disruption contributed to the chronic migraine (CM). The overexpression of SIRT1 through virus injection and SRT1720 administration both demonstrated the effect of alleviating the key link of CM mechanisms, including central sensitization and inflammatory activation in the trigeminal nucleus and circadian rhythms disruption. Moreover, the anti-inflammatory effect was further demonstrated to be mediated by BMAL1 by using shRNA."

Journal • CNS Disorders • Inflammation • Migraine • Pain • ARNTL • BMAL1 • FOS • SIRT1

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

SRT1720 ameliorates LPS-induced depressive-like behaviors in mice and activates Parkin-mediated mitophagy. (PubMed, BMC Neurosci) - "These findings suggested that activation of SIRT1 could alleviate depressive-like behaviors in mice following LPS challenge, potentially through a Parkin-dependent mitophagy mechanism."

Journal • Preclinical • CNS Disorders • Depression • Metabolic Disorders • Psychiatry

Activation of Sirt1 protects from single-walled carbon nanotubes-induced pulmonary fibrosis by inhibiting alveolar macrophage senescence. (PubMed, Ecotoxicol Environ Saf) - "Our study reveals that Sirt1-dependent AMs senescence regulates SWCNT-provoked pulmonary fibrosis, and activation of Sirt1 could be a promising therapeutic target."

Journal • Immunology • Pulmonary Disease • Respiratory Diseases • SIRT1

SIRT1-mediated deacetylation and activation of MEK/ERK pathway decreased IL-6 in spinal dorsal horn to promote oxycodone tolerance. (PubMed, Neuropharmacology) - "An SIRT1 agonist (SRT1720) inhibited the development of oxycodone tolerance, suppressed IL-6 overexpression, normalized H3K9ac and phospho-ERK/MEK levels, and reduced H3K9ac expression at the IL-6 promoter. Thus, SIRT1 promotes oxycodone tolerance by deacetylating histone H3K9 at the IL-6 promoter and activating the MEK/ERK pathway to upregulate IL-6 expression."

Journal • Pain • IL6 • MAP2K1 • SIRT1 • SIRT7

SIRT1 and its SUMOylation attenuate hyperoxia-induced lung injury by improving mitochondrial biogenesis and fusion. (PubMed, Free Radic Biol Med) - "Hyperoxia increases ROS levels to decrease SIRT1 and SUMO1 levels, thereby inhibiting mitochondrial biogenesis and fusion, and promotion of SIRT1 and its SUMOylation improves mitochondrial biogenesis and fusion, thereby attenuating hyperoxia lung injury."

Journal • Bronchopulmonary Dysplasia • Ocular Inflammation • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • MFN2 • NRF1 • SIRT1 • TFAM