GYY4137 / National University of Singapore - LARVOL DELTA

Use of a Near Infrared Probe to Assess Intracellular Hydrogen Sulfide Production. (PubMed, J Surg Res) - "This NIR-HS probe was shown to be a useful compound in the detection of H2S in cell-free and cellular environments. Further studies are needed to demonstrate its use within in vivo applications of specific ischemic and inflammatory disease models prior to clinical translation."

Journal • Inflammation

Self-activated prodrug nanocomposites reprogramming lactic acid metabolism to initiate acidosis-endoplasmic reticulum stress cascade and potentiate immunogenic cell death for enhanced liver cancer therapy. (PubMed, J Nanobiotechnology) - "This system is self-assembled from a pentavalent arsenate prodrug (AsO₄³⁻), the hydrogen sulfide (H₂S) donor GYY4137, and the lactate export inhibitor diclofenac (DCF), enabling precise responsiveness to the acidic and reductive tumor microenvironment...This is evidenced by the release of damage-associated molecular patterns (DAMPs), dendritic cell maturation, and T cell activation. By integrating lactate metabolism regulation, prodrug activation, and immune remodeling, this strategy provides a promising avenue for combined chemo-immunotherapy of HCC."

Journal • Hepatocellular Cancer • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor • ATF4 • HSPA5

Hydrogen Sulfide Attenuates Cisplatin-Induced Acute Kidney Injury via Dual Inhibition of Apoptosis and Pyroptosis. (PubMed, Biomedicines) - "Purpose: Cisplatin chemotherapy is complicated by acute kidney injury (cis-AKI), driven by regulated cell death pathways, including apoptosis and pyroptosis. It suppressed both the early apoptotic and delayed pyroptosis cascades without reversing CBS downregulation. GYY4137 mitigated both apoptosis and pyroptosis, offering a promising multi-targeted therapy for cis-AKI."

IO biomarker • Journal • Acute Kidney Injury • Inflammation • Nephrology • Renal Disease • BAX • BCL2 • CASP3 • GSDME • IL18 • IL1B • NLRP3

Hydrogen sulfide improves vascular endothelial function in hypertensive states through SIRT6 anti-inflammatory signaling. (PubMed, Acta Biochim Biophys Sin (Shanghai)) - "Using an angiotensin II (Ang II)-induced endothelial dysfunction model, we show that treatment with the hydrogen sulfide (H₂S) donor GYY4137 significantly reverses Ang II-induced damage...Critically, SIRT6 inhibitors block the protective effects of H₂S in the endothelium. This study demonstrates that H₂S protects vascular endothelial function by activating the SIRT6 anti-inflammatory pathway."

Journal • Cardiovascular • Hypertension • Inflammation • ICAM1 • IL6 • SIRT6

pH-responsive Oral liposomal delivery of hydrogen sulfide donor GYY4137 enables colon-targeted therapy for inflammatory bowel disease. (PubMed, J Nanobiotechnology) - "These findings demonstrate that Oral H₂S lipo enables effective, site-specific delivery of H₂S to inflamed colonic tissue, offering a clinically relevant platform to overcome limitations of conventional H₂S donor therapies in IBD management."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

Expression and activity of the umami taste receptor (TAS1R1/TAS1R3) in rat corpus cavernosum. (PubMed, Eur J Pharmacol) - "Isometric force recordings for the TAS1R1/TAS1R3 agonist monosodium glutamate (MSG), the NO donor SNAP, the hydrogen sulfide (H2S) donor GYY 4137, and electrical field stimulation (EFS) and measured endogenous H2S production...These findings indicate significant neuronal and endothelial expression of TAS1R1/TAS1R3 in the CC and DPA, where MSG promotes SM relaxation. In the CC, MSG enhances nerve-mediated relaxation induced by NO and H2S and stimulates H2S production, suggesting TAS1R1/TAS1R3 as a potential therapeutic target for ED."

Journal • Preclinical • Erectile Dysfunction

The CBS/H2S axis regulates intestinal stem cell homeostasis and radiation-induced intestinal damage. (PubMed, Stem Cell Res Ther) - "Our findings suggest that the CBS/H2S axis contributes to the regulation of ISC homeostasis and represents a potential target for radiation protection, mediated through the intervention of non-epithelial cells."

Journal • Gastrointestinal Disorder

The role of H2S in isoproterenol-induced cardiac hypertrophy: A comparative study using slow releaser GYY4137 and a newly synthetized fast releaser BM-112. (PubMed, Biomed Pharmacother) - "We identified impaired autophagic flux in the presence of ISO and BM-112. However, GYY4137 treatment promoted autophagy beyond basal levels.Taken together, GYY4137, but not BM-112, successfully prevented adrenergic overstimulation-induced hypertrophy by reducing oxidative stress, mitigating mitochondrial dysfunction, and enhancing autophagic flux."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders

Effect of Slow Release Hydrogen Sulfide Donor GYY4137 on Vascular Smooth Muscle and Endothelial Response in an In Vitro Ischemia-Reperfusion Model of Rat Thoracic Aorta. (PubMed, Can J Physiol Pharmacol) - "In conclusion, GYY4137 reduces oxidative stress and apoptosis markers without improving vascular dysfunction in an IR model of rat thoracic aorta. This disparity underscores the complex pathophysiology of vascular IR injury, where cellular-level protection does not readily translate to functional recovery."

Journal • Preclinical • Cardiovascular • Reperfusion Injury • CASP3

Hydrogen sulfide in placental development and pregnancy disorders: mechanisms, therapeutic potential, and translational challenges. (PubMed, Reprod Biol Endocrinol) - "Additionally, exogenous H₂S donors (e.g., GYY4137 and NaHS) have demonstrated therapeutic potential in experimental models, effectively reversing PE-like pathologies, improving placental perfusion, and restoring trophoblast function...As research continues to reveal H₂S-mediated mechanisms in placental function and pregnancy disorders, optimizing the pharmacological application and clinical translation of H₂S donors and combination therapies will be a key research focus. Advancing H₂S metabolic regulation, signaling pathways, and targeted delivery systems may drive the development of novel diagnostic tools and therapeutic strategies for pregnancy complications."

Journal • Review • Gynecology • NOS3

Reactive Sulfur Species and Protein Persulfidation: An Emerging Redox Axis in Human Health and Disease. (PubMed, Curr Issues Mol Biol) - "Therapeutically, slow-release donors (SG1002, GYY4137), mitochondria-targeted vectors (AP39), photo- or thiol-activated "smart" scaffolds, diet-derived polysulfides/isothiocyanates and microbiota engineering aim to restore the protective RSS window. Key challenges are a narrow therapeutic margin and real-time quantification of persulfide fluxes. Harnessing RSS therefore offers a route to rebalance redox homeostasis across diverse chronic diseases."

Journal • Review • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Metabolic Disorders • Novel Coronavirus Disease • Oncology • Sarcopenia • GAPDH • KEAP1 • NLRP3

Hydrogen Sulfide Deficiency Contributes to Tubular Damage and Calcium Oxalate Crystal Formation in Hyperoxaluria Nephropathy: Role of Osteopontin and Tamm-Horsfall Protein. (PubMed, Antioxidants (Basel)) - "Chronic supplementation with the H2S donor GYY4137 (GYY) significantly attenuated HP-induced tubular injury and CaOx deposition by reducing OPN and THP secretion...Mechanistically, oxalate activated cyclic AMP/protein kinase A (PKA) signaling, which promoted OPN and THP secretion; these effects were eradicated by the PKA inhibitor H89 or GYY. These findings indicate that hyperoxaluria impairs Sp1 transcriptional activity, resulting in H2S deficiency and compromised anticrystallization defense in oxalate-induced tubulopathy."

Journal • Nephrology • Renal Calculi • Renal Disease • SPP1

Hydrogen Sulfide-Preconditioned Mesenchymal Stem Cells Attenuate Ferroptosis in Corneal Alkali Burn via the AMPK/Nrf2/HO-1 Pathway in an IL-10-Dependent Manner. (PubMed, Invest Ophthalmol Vis Sci) - "MSCs were treated with various concentrations of GYY4137 (an H2S donor) and Western blot was used to detect the expression of IL-10 and cleaved-caspase-3. Knockdown of IL-10 via siRNA attenuated the inhibitory effects of H2S-MSC on erastin-induced ferroptosis in HCECs. H2S preconditioning augmented the anti-inflammatory and anti-ferroptotic effects of MSCs via activation of the AMPK/Nrf2/HO-1 pathway in an IL-10-dependent way, offering a novel strategy for corneal alkali burn treatment."

Journal • Corneal Abrasion • CASP3 • GPX4 • IL10 • SLC7A11

Effect of H2S on endothelial barrier function impairment in anorectal vascular plexus caused by deoxycholic acid. (PubMed, Front Med (Lausanne)) - "GYY4137 can also increase resistance to SDC-induced VEBF injury and improve the distribution of TJPs in the AVP in mouse model. GYY4137 can improve the distribution of TJPs by inhibiting the activation of the MLCK-P-MLC2 signaling pathway induced by DCA, thereby protecting the VEBF in AVP, which may be applied to hemorrhoids therapy in the future."

Journal • Gastroenterology • Gastrointestinal Disorder • MYLK

The role of hydrogen sulphide in TGF-β1-induced pulmonary fibrosis in human lung tissues (ERS 2025) - "To assess the therapeutic effects of exogenous H2S treatments, rapid H 2 S-releasing donor NaHS (100μM), slow H 2 S-releasing donor GYY4137 (100-300μM), mitochondria-targeted slow H 2 S-releasing donor AP39 (30-100nM) and pirfenidone were used. Further studies are needed to confirm these findings in vivo. Supported by Health Institutes of Türkiye (TUSEB-Project No:4569) and The Scientific and Technological Research Council of Türkiye (TUBITAK-Project No:1919B012300703)."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • TGFB1

Mechanisms and therapeutic potential of hydrogen sulfide in traumatic central nervous system injuries. (PubMed, Med Gas Res) - "Further, it mitigates oxidative stress by activating the nuclear factor erythroid 2-related factor 2 and mechanistic target of the rapamycin pathway, and inhibiting glutamate-mediated damage...Emerging H₂S delivery strategies, including slow-releasing donors such as GYY4137 and advanced hydrogel-based systems, address challenges in achieving sustained and targeted therapeutic effects. Although preclinical evidence has demonstrated the promise of H₂S-based therapies, further research is required to optimize delivery methods, investigate concentration-dependent effects, and validate clinical efficacy. This review provides a comprehensive foundation for advancing H₂S as a therapeutic agent in traumatic central nervous system injuries."

Journal • CNS Disorders • Inflammation • Musculoskeletal Diseases • Orthopedics • Vascular Neurology

Hydrogen sulfide ameliorates peritoneal fibrosis: inhibition of high mobility group box-1 expression to block the activation of the transforming growth factor-beta/Smad3 pathway. (PubMed, Med Gas Res) - "A peritoneal fibrosis model was established through the intraperitoneal injection of 0.1% chlorhexidine gluconate. Subsequently, the mice were administered an intraperitoneal injection of the H2S donor GYY4137. The experimental data indicate that H2S mitigates the progression of peritoneal fibrosis, potentially by inhibiting the expression of high mobility group box-1 and consequently blocking the activation of the (TGF-β)/Smad3 signaling pathway. This study provides a scientific basis for the future clinical application of H2S in the treatment of peritoneal fibrosis."

Journal • Fibrosis • Immunology • HMGB1 • SMAD3 • TGFB1

Slow-releasing hydrogen sulfide donor GYY4137 induces epithelial-mesenchymal transition in A549 human lung adenocarcinoma cells. (PubMed, J Toxicol Sci) - "Transcriptome analysis of cells exposed to 3 mM GYY4137 for 6 days indicated ER stress and epithelial-mesenchymal transition (EMT), the latter confirmed by qRT-PCR, immunoblot, and immunocytochemical analyses. These results show the possible roles of EMT in the homeostasis of pulmonary epithelial cells during exposure to H2S."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Hydrogen sulfide replenishment ameliorates impaired platelet response to clopidogrel in mice with experimental diabetes mellitus. (PubMed, Xenobiotica) - "Body weight gain, blood glucose, glucose tolerance, insulin tolerance, blood H2S, adenosine diphosphate (ADP)-induced whole-blood platelet aggregation, main clopidogrel metabolites (active thiol metabolite H4 and inactive clopidogrel carboxylate) in plasma, and the expression of main clopidogrel-metabolizing enzymes and interleukin-1β as well as their genes in the liver were measured, respectively.Compared with control mice, DM mice exhibited significant decreases in plasma H2S and H4 levels, glucose tolerance, insulin sensitivity, and clopidogrel-metabolizing enzyme expression, but significant increases in blood glucose, ADP-induced whole-blood platelet aggregation, and hepatic interleukin-1β expression, respectively. After use of GYY4137, boosting blood H2S levels ameliorated or reversed all other changes observed in DM mice, except for blood glucose elevation.Blood H2S reduction may contribute to impaired platelet inhibition of clopidogrel in DM mice, suggesting that..."

Journal • Preclinical • Diabetes • Metabolic Disorders • IL1B

cth-2/mpst-1-dependent H2S deficiency enhances acrylonitrile acute toxicity in Caenorhabditis elegans. (PubMed, Neurotoxicology) - "In contrast, H2S donor GYY4137 significantly attenuated the AN-damaged survival rate, body bends, and dopaminergic neuron morphology. Our findings demonstrated that the reduction of H2S mediates the acute toxicity of acrylonitrile."

Journal

Exogenous H2S reduces oxidative stress induced by lipid mixture in HepG2 cells through USP22/SIRT1 axis. (PubMed, Sci Rep) - "HepG2 cells were stimulated with LM with or without GYY4137 (200 µM) treatment for 24 h...After USP22 was knocked down, the efficacy of exogenous H2S on mitigating LM-induced oxidative damage and inflammatory reaction in HepG2 cells had been weakened. In conclusion, exogenous H2S inhibited SIRT1 ubiquitination degradation through USP22, thereby alleviating LM-induced oxidative stress and inflammatory responses in HepG2 cells."

Journal • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Targeted Protein Degradation • IL6 • SIRT1 • TNFA • USP22

A Slow Hydrogen Sulfide Donor GYY-4137 Partially Improves Vascular Function in Spontaneously Hypertensive Rats Fed a High-Fat Diet. (PubMed, Pathophysiology) - "A slow H2S-releasing donor could partially ameliorate the metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the NO signaling restoration and suppression of inflammation."

Journal • Preclinical • Cardiovascular • Hypertension • Metabolic Disorders • Obesity • Oncology • TNFA

GYY4137, a Slow-Releasing Hydrogen Sulfide Donor, Attenuates Skeletal Muscle Abnormalities in a Murine Model of Duchenne Muscular Dystrophy. (PubMed, Antioxid Redox Signal) - "Redox Signal. 00, 000-000."

Journal • Preclinical • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy • CASP3 • HMOX1 • SPP1

Hydrogen Sulfide (H2S) Alleviates Hyperoxia-induced Changes In Intracellular Calcium Regulation In Human Fetal Airway Smooth Muscle (ATS 2025) - "fASM were treated 24-72 hours with H2S donor GYY4137, mitochondrial-specific H2S donor AP39, cystathione-β-synthase (CBS) stabilizer AdoMet, cAMP inhibitors SQ22536 or KT5720, or vehicle control (DMSO)...Our findings suggest hyperoxia leads to [Ca2+]i and [Ca2+]m dysfunction in developing airway cells, which can be alleviated through modulation of H2S pathways, offering potential targets for future therapies to blunt hyperoxia effects on bronchoconstriction and bronchodilation. Acknowledgment: Supported by AHA Postdoctoral Fellowship 20POST35210002 (Bartman), NIH R01 HL-056470 (Prakash), and HL-160570 (Pabelick)."

Asthma • Immunology • Respiratory Diseases • RHOD

Hydrogen sulfide preserves intestinal barrier repair function through sulfhydration of RPS20 in experimental colitis. (PubMed, Sci Rep) - "We recognized that exogenous H2S donor-GYY4137 significantly alleviated the symptoms in UC mice models and maintained Minichromosome Maintenance Complex Component 2 (MCM2) expression...Cell experiments indicated that the expression of RPS20-ssh, rather than total expression of RPS20, is responsible.Our investigation indicated that CBS-H2S axis increases the sulfhydration level of RPS20, leading to enhanced binding between RPS20 and MCM2 mRNA, thereby promoting intestinal epithelial proliferation. This may provide a novel therapeutic strategy for the clinical treatment of colitis."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • MCM2