sodium polysulthionate (SG1002) / Sulfagenix - LARVOL DELTA

Hydrogen sulfide protects erectile function through stimulation of antioxidant defense in the corpus cavernosum. (PubMed, bioRxiv) - "Txnip was reciprocally increased in CSE -/- mice and decreased by SG1002 treatment. These data suggest that H 2 S positively influences erectile function and penile free radical balance, likely through augmentation of the glutathione and thioredoxin endogenous antioxidant systems."

Journal • Erectile Dysfunction • Genetic Disorders • Obesity • GPX1 • GPX4 • GSTM1 • HMOX1 • NQO1 • TXNIP

Chronic administration of the hydrogen sulfide prodrug SG1002 partially protects against erectile dysfunction resulting from long-term androgen deprivation. (PubMed, bioRxiv) - "SG1002 partially protected against castration-induced fibrotic remodeling of the IPA. H 2 S therapy provides a modest but potentially clinically relevant protection of erectile function and health of the erectile structures against the harshly damaging effects of chronic androgen deprivation."

Journal • Cardiovascular • Erectile Dysfunction • Fibrosis • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Cth/Mpst double ablation results in early onset fatty liver disease in lean mice. (PubMed, Redox Biol) - "Sulfide donor (SG1002) treatment attenuated the fatty liver disease of CTH/MPST-deficient mice. Our findings underline the importance of endogenously produced H2S in the pathogenesis of MAFLD and introduce the Cth/Mpst-/- mouse as a new animal model of early onset hepatic steatosis."

Journal • Preclinical • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • PPARA

EVALUATION OF TISSUE LIPID PROFILES IN A MOUSE MODEL OF DOXORUBICIN-INDUCED CARDIOTOXICITY COMPLICATED BY HYPERTENSION - Mallika Datta (ACC 2025) - "Background: Doxorubicin (DOX) is associated with declines in left ventricular ejection fraction (LVEF), which is exacerbated by hypertension (HTN). SG1002 alleviates DOX cardiotoxicity in HTN. Inverse relationships between cardiac sphingomyelins and ceramides were observed in cardiac injury. Plasma ceramide and sphingolipid levels may predict adverse cardiac outcomes, as indicated by significant correlations between cardiac function and lipidomic data."

Preclinical • Cardiovascular • Hypertension

Adjunctive therapy with an oral H2S donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction. (PubMed, Br J Pharmacol) - "SGLT2i monotherapy remediated pathological complications exhibited by two well-established HFpEF models. Adjunctive H2S therapy resulted in further improvements of cardiometabolic perturbations beyond SGLT2i monotherapy. Follow-up SG1002 monotherapy studies inferred an improved phenotype with combination therapy beyond either monotherapy. These data demonstrate the differing effects of SGLT2i and H2S therapy while also revealing the superior efficacy of the combination therapy in cardiometabolic HFpEF."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Obesity

Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used. (PubMed, Geroscience) - "Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging."

Journal • Preclinical

Hydrogen Sulfide Attenuates Duchenne Cardiomyopathy via Suppression of Sterile Inflammation (AHA 2023) - "Our results demonstrate that early treatment with SG1002 preserves cardiac function in a mouse model of DMD and suggest a potential therapeutic role of NLRP3 inflammasome suppression as a protective strategy in DMD."

Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Heart Failure • Inflammation • Muscular Dystrophy • NLRP3

Hydrogen Sulfide Donor, SG1002, Protects Against Hypertension-Induced Exacerbation of Doxorubicin Cardiotoxicity in Female Mice (AHA 2022) - "Our results in female mice indicate that HTN worsens DOX-induced cardiomyopathy, which is attenuated with SG1002 treatment. Interestingly, SG1002 also prevented HTN following ATII infusion in female mice. Further studies are warranted to determine the efficacy of the H2S donor, SG1002 to prevent DOX-associated LVEF declines in mice with and without HTN."

Preclinical • Breast Cancer • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Leukemia • Lymphoma • Myocardial Infarction

HS Prodrug, SG-1002, Protects against Myocardial Oxidative Damage and Hypertrophy In Vitro via Induction of Cystathionine β-Synthase and Antioxidant Proteins. (PubMed, Biomedicines) - "Treatment with SG-1002 caused a significant induction of cell viability and a marked reduction of cellular cytotoxicity in HL-1 cells under serum starvation incubated without or with HO. Experimental results of this study suggest that SG-1002 attenuates myocardial cellular oxidative damage and/or hypertrophic signaling via increasing HS levels or HS producing enzymes, CBS, and antioxidant proteins."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • CAT • NPPB • SOD1 • TGFB1 • TIMP1

[VIRTUAL] Hydrogen Sulfide Donor, SG1002, Preserves Left Ventricular Global Function and Contractile Reserve in a Mouse Model of Doxorubicin Cardiotoxicity (AHA 2021) - "Our results indicate that LV GLS and cardiac contractile reserve are able to detect early changes in LV contractility due to cardiotoxicity following DOX treatment, which can be prevented with SG1002. This further highlights the importance of early screening with advanced imaging to identify signs of cardiotoxicity."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Immunology • Inflammation • Metabolic Disorders • Myocardial Infarction

[VIRTUAL] Mapping the endothelial cell S-Sulfhydrome highlights the crucial role of integrin sulfhydration in vascular function (ESC 2021) - "Functional studies includedendothelial cell adhesion, shear stress-induced cell alignment, blood pressure measurements andflow-induced vasodilatation in endothelial cell-specific CSE knock out mice and a smallcollective of patients with endothelial dysfunction. Three paired sample sets were compared: (1) native human endothelial cells isolatedfrom plaque-free mesenteric arteries (CSE activity high) and plaque-containing carotid arteries(CSE activity low), (2) cultured human endothelial cells kept under static conditions or exposedto fluid shear stress to decrease CSE expression, and (3) cultured endothelial cells exposed toshear stress to decrease CSE expression and treated with solvent or the slow-releasing H2Sndonor, SG1002... Vascular disease is associated with marked changes in the S-sulfhydration ofendothelial cell proteins involved in mediating responses to flow. Short term H2Snsupplementation improved vascular reactivity in humans highlighting the potential of..."

Atherosclerosis • Cardiovascular • Dyslipidemia

Mapping the Endothelial Cell S-Sulfhydrome Highlights the Crucial Role of Integrin Sulfhydration in Vascular Function. (PubMed, Circulation) - " Three paired sample sets were compared: (1) native human endothelial cells isolated from plaque-free mesenteric arteries (CSE activity high) and plaque-containing carotid arteries (CSE activity low), (2) cultured human endothelial cells kept under static conditions or exposed to fluid shear stress to decrease CSE expression, and (3) cultured endothelial cells exposed to shear stress to decrease CSE expression and treated with solvent or the slow-releasing HS donor, SG1002... Vascular disease is associated with marked changes in the S-sulfhydration of endothelial cell proteins involved in mediating responses to flow. Short term HS supplementation improved vascular reactivity in humans highlighting the potential of interfering with this pathway to treat vascular disease."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

SG1002 AND CATENATED DIVALENT ORGANIC SULFUR COMPOUNDS AS PROMISING HYDROGEN SULFIDE PRODRUGS. (PubMed, Antioxid Redox Signal) - "Although hydrogen sulfide (H2S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H2S/SS in blood and/ or tissues, and are amenable to treatment by H2S supplementation, development of safe and efficacious H2S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents."

Journal

Assessing the Safety and Ability of SG1002 to Overcome Deficits in Hydrogen Sulfide in Heart Failure Patients (clinicaltrials.gov) - P=N/A; N=16; Completed; Sponsor: Sulfagenix Australia Pty Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Cardiovascular • Congestive Heart Failure • Heart Failure

Effects of a novel hydrogen sulfide prodrug in a porcine model of acute limb ischemia. (PubMed, J Vasc Surg) - "Our results suggest that daily administration of the HS prodrug, SG-1002, leads to an increase in circulating HS and nitric oxide signaling and preserves vessel number and density in ischemic limbs. Furthermore, SG-1002 therapy improved endothelial-dependent coronary artery vasorelaxation in the setting of ALI. Our data demonstrate that SG-1002 preserves the vascular architecture in ischemic limbs and exerts vascular protective effects in the coronary vasculature in a model of peripheral vascular disease."

Journal • Preclinical

Hydrogen Sulfide Protects the Heart Against Homocysteine-Induced Remodeling by Regulating Autophagy and Pyroptosis (BCVS 2019) - "...We treated CBS+/- mice (a model of HHcy) and WT mice with SG1002 (slow-releasing H2S donor) or control diet for 14 weeks and performed deep sequencing of their hearts (LV tissue)...We conclude that H2S could alleviate cardiac remodeling by inducing autophagy and inhibiting NF-kB-mediated pyroptosis. This is the first report that H2S controls cross-talk of cardiac pyroptosis and autophagy."

Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK. (PubMed, J Mol Cell Cardiol) - "Together, these results suggest that hydrogen sulfide is an important regulator of cardiac mitochondrial content and establishes that exogenous hydrogen sulfide can induce mitochondrial biogenesis via an AMPK-PGC1α signaling cascade."

Journal

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cardiac Remodeling and Dysfunction. (PubMed, Front Physiol) - "These results demonstrate SG1002 treatment alleviates cardiac remodeling and afterload in HHcy mice. HS may be cardioprotective in conditions where HS is reduced and Hcy is elevated."

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