SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Gojon, Gabriel; Morales, Guillermo A

doi:10.1089/ars.2020.8060

Cited by 22 publications

(15 citation statements)

References 280 publications

(369 reference statements)

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“…Third, decreased AII amacrine cells numbers in OXYS rats’ retina after TC-2153 treatment may be a possible compensatory change that is not directly related to STEP. Finally, TC-2153 is considered a potential H 2 S donor capable of modulating the cell’s redox homeostasis dysfunction [ 50 ], which also contributes to AMD pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

Telegina

Kulikova

Kozhevnikova

et al. 2020

IJMS

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Tyrosine phosphatase STEP (striatal-enriched tyrosine protein phosphatase) is a brain-specific protein phosphatase and is involved in the pathogenesis of many neurodegenerative diseases. Here, we examined the impact of STEP on the development of age-related macular degeneration (AMD)-like pathology in senescence-accelerated OXYS rats. Using OXYS and Wistar rats (control), we for the first time demonstrated age-dependent changes in Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the retina. The increases in STEP protein levels and the decrease of total and STEP phosphatase activities in the retina (as compared with Wistar rats) preceded the manifestation of clinical signs of AMD in OXYS rats (age 20 days). There were no differences in these retinal parameters between 13-month-old Wistar rats and OXYS rats with pronounced signs of AMD. Inhibition of STEP with TC-2153 during progressive AMD-like retinopathy (from 9 to 13 months of age) reduced the thickness of the retinal inner nuclear layer, as evidenced by a decreased amount of parvalbumin-positive amacrine neurons. Prolonged treatment with TC-2153 had no effect on Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the OXYS retina. Thus, TC-2153 may negatively affect the retina through mechanisms unrelated to STEP.

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“…This leads to the suggestion that agents able to activate the Nrf2 system and induce sustained antioxidant activity may represent a useful strategy to counteract the viral infection by respiratory viruses (Komaravelli & Casola, 2014). As reported above, many H 2 S‐releasing agents evoke significant protective effects against oxidative stress in the host cells, which are mediated by H 2 S and/or related sulfane sulfur through well‐clarified mechanisms, such as increased nuclear translocation of Nrf2 and inhibition of NADPH oxidase enzymes (Gojon & Morales, 2020).…”

Section: H2s and Viral Infectionsmentioning

confidence: 95%

Section: Endogenous H Smentioning

confidence: 99%

“…Moreover, H 2 S is endowed with direct antioxidant activity, thus protecting the tissues from the oxidative stress. (d) H 2 S activates K ATP channels expressed on the cell membrane of bronchial smooth muscle cells, promoting bronchodilation, and blocks the Na + /K + ATPase pump, triggering electrolyte absorption and enhancing mucociliary clearance Besides the triggering of the "antioxidant machinery" directly attributable to H 2 S, other "indirect" effects are also involved in antioxidant activity of H 2 S. For instance, H 2 S contributes to the maintenance of elevated levels of GSH, which is one of the main intracellular antioxidant compounds and an effective scavenger of reactive species (Gojon & Morales, 2020). GSH can itself be another player with antiviral effects.…”

Section: H 2 S and Viral Infectionsmentioning

confidence: 99%

“…As defective endogenous production of H 2 S has been associated with many systemic disorders, great efforts have been directed to the development of effective pharmacological agents able to increase H 2 S levels. The pharmacological modulation of H 2 S is a dynamic field in recent drug discovery research, which has been well‐examined and reported in some seminal reviews (Gojon & Morales, 2020; Szabo & Papapetropoulos, 2017; Zheng et al, 2018). Presently, a large number of natural and synthetic compounds have been recognized as effective H 2 S donors (Keyaerts et al, 2004; Sardu et al, 2020), and some of them are in clinical trials for the treatment of cardiovascular diseases (SG‐1002 for heart failure) (Polhemus et al, 2015) and cancer disease (sulforaphane [SFN]) (Jiang et al, 2018).…”

Section: Endogenous H2smentioning

confidence: 99%

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Anti‐inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H₂S donors in COVID‐19 therapy

et al. 2020

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The COVID-19 pandemic caused by SARS-Cov-2 demands rapid, safe and effective therapeutic options. In the last decades, the endogenous gasotransmitter hydrogen sulfide (H 2 S) has emerged as modulator of several biological functions and its deficiency has been associated with different disorders. Therefore, many H 2 S-releasing agents have been developed as potential therapeutic tools for diseases related with impaired H 2 S production and/or activity. Some of these compounds are in advanced clinical trials. Presently, the pivotal role of H 2 S in modulating the inflammatory response and pro-inflammatory cytokine cascade is well recognized, and the usefulness of some H 2 S-donors for the treatment of acute lung inflammation has been reported. Recent data is elucidating several mechanisms of action, which may account for antiviral effects of H 2 S. Noteworthy, some preliminary clinical results suggest an inverse relationship between endogenous H 2 S levels and severity of COVID-19. Therefore, repurposing of H 2 S-releasing drugs may be a potential therapeutic opportunity for treatment of COVID-19.

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SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Cited by 22 publications

References 280 publications

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

Anti‐inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H₂S donors in COVID‐19 therapy

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SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

Cited by 22 publications

References 280 publications

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

Anti‐inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H2S donors in COVID‐19 therapy

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Anti‐inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H₂S donors in COVID‐19 therapy