GYY4137 / National University of Singapore - LARVOL DELTA

Hydrogen sulfide alleviates hyperoxia effects on mitochondria in human developing airway smooth muscle. (PubMed, JCI Insight) - "Human fetal ASM (fASM) were exposed to moderate hyperoxia to investigate the effects of exogenous H₂S donors (GYY4137, AP39) and stabilization of cystathionine β-synthase (CBS), an H₂S biosynthetic enzyme, on mitochondrial structure and function. Hyperoxia impaired fASM mitochondrial integrity, while H₂S donors in particular, or CBS stabilization attenuated adverse O2 effects on mitochondrial morphology, reactive oxygen species, respiration, calcium regulation, and contractility. These findings highlight the therapeutic potential of H₂S in the premature lung exposed to moderate hyperoxia."

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

Therapeutic Potential of GYY4137 in Reducing Oxidative Stress and Mortality in Experimental Decompression Sickness. (PubMed, Sci Rep) - No abstract available

Journal

A Protective Role of Hydrogen Sulfide Donor GYY4137 Through Activated Microglia-induced Anti-inflammatory Cytokines in the Spinal Cord of Diabetic Rats. (PubMed, Mol Neurobiol) - "The treatment also prevented the loss of astrocytes and neuronal cells in the spinal cord, indicating neuroprotective effects. In conclusion, our findings suggest that H₂S can shift microglial activity from neuroinflammation to neuroprotection, highlighting its potential as a possible candidate for novel therapeutic strategy for diabetes and its complications."

Journal • Preclinical • Diabetes • Diabetic Neuropathy • Inflammation • Metabolic Disorders • Pain • IL10 • IL12A • IL13 • STAT3 • TGFB1

Investigation of organosulfur molecules in experimental acute pancreatitis: Antioxidant and antiferroptotic actions of ATB-346. (PubMed, Biomed Pharmacother) - "Our results indicate that ATB-346 possesses anti-inflammatory and cytoprotective properties, thus making it a promising candidate in the treatment of AP."

Journal • Inflammation • Pancreatitis • GPX4

Hydrogen sulfide in ocular physiology and pathology: molecular Mechanisms, therapeutic Paradoxes, and delivery challenges. (PubMed, Mol Biol Rep) - "A central translational challenge is designing controlled-release H₂S donors (e.g., GYY4137, ACS67) that replicate physiological signaling while overcoming formidable ocular bioavailability barriers. We evaluate advanced delivery platforms, from in situ gels to nanoparticle systems, that promise targeted and sustained release. By integrating molecular mechanisms with a critical appraisal of conflicting evidence, this review establishes a conceptual framework for H₂S-based therapeutics and highlights unresolved mechanistic questions and delivery hurdles that must be addressed to realize clinical potential."

Journal • Review • Diabetic Retinopathy • Glaucoma • Ophthalmology • Retinal Disorders

Endogenous H₂S promotes HSPA8 sulfhydration to downregulate HIF1α and prevent ferroptosis in septic myocardial injury. (PubMed, Redox Rep) - "We used in vitro and in vivo sepsis models we investigated the protective to examine the effects of H₂S donors (GYY4137 and Allicin) on SIMI...This study reveals a novel H₂S-HSPA8-HIF1α-BNIP3 axis in regulating ferroptosis and myocardial injury during sepsis. Protein sulfhydration mediates the cardioprotective effects of H₂S, and Allicin emerges as a promising therapeutic agent for septic cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Septic Shock • HIF1A • HSPA8

Cystathionine γ-lyase-dependent S-sulfhydration of Smad3: A novel target to alleviate fibrosis in systemic sclerosis. (PubMed, Arthritis Rheumatol) - "Smad3 S-sulfhydration mediates the antifibrotic effect of CSE in SSc, highlighting it as a critical mechanism and promising therapeutic target."

Journal • Fibrosis • Immunology • Respiratory Diseases • Scleroderma • Systemic Sclerosis • SMAD3 • TGFB1

Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review. (PubMed, Int J Mol Sci) - "Organic donors (e.g., GYY4137, ACS67, ACS84, SPRC, ADT-OH and its derivatives, S-memantine, and MTC) provide sustained H2S release, stabilize the blood-brain barrier, and exhibit antiapoptotic activity. The analysis reveals a general pattern: all classes of H2S donors effectively modulate key pathological mechanisms, differing in their rate, duration, and specificity of action. These findings highlight the therapeutic promise of H2S-based pharmacological agents in clinical neurotraumatology, while emphasizing the need for further research to optimize delivery systems, enhance efficacy, and minimize adverse effects."

Journal • Review • Cardiovascular • CNS Disorders • Inflammation • Neuralgia • Orthopedics • Pain • Vascular Neurology

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