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A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients

Recent studies demonstrate robust molecular cross talk and signaling between hydrogen sulfide (H(2)S) and nitric oxide (NO). Heart failure (HF) patients are deficient in both H(2)S and NO, two molecules that are critical for cardiovascular homeostasis. A phase I clinical trial of a novel H(2)S prodr...

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Autores principales: Polhemus, David J., Li, Zhen, Pattillo, Christopher B., Gojon, Gabriel, Giordano, Tony, Krum, Henry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034803/
https://www.ncbi.nlm.nih.gov/pubmed/25930144
http://dx.doi.org/10.1111/1755-5922.12128
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author Polhemus, David J.
Li, Zhen
Pattillo, Christopher B.
Gojon, Gabriel
Gojon, Gabriel
Giordano, Tony
Krum, Henry
author_facet Polhemus, David J.
Li, Zhen
Pattillo, Christopher B.
Gojon, Gabriel
Gojon, Gabriel
Giordano, Tony
Krum, Henry
author_sort Polhemus, David J.
collection PubMed
description Recent studies demonstrate robust molecular cross talk and signaling between hydrogen sulfide (H(2)S) and nitric oxide (NO). Heart failure (HF) patients are deficient in both H(2)S and NO, two molecules that are critical for cardiovascular homeostasis. A phase I clinical trial of a novel H(2)S prodrug (SG1002) was designed to assess safety and changes in H(2)S and NO bioavailability in healthy and HF subjects. Healthy subjects (n = 7) and heart failure patients (n = 8) received oral SG1002 treatment in escalating dosages of 200, 400, and 800 mg twice daily for 7 days for each dose. Safety and tolerability were assessed by physical examination, vital signs, and ECG analysis. Plasma samples were collected during a 24‐h period each week for H(2)S and NO analysis. BNP and glutathione levels were analyzed as markers of cardiac health and redox status. Administration of SG1002 resulted in increased H(2)S levels in healthy subjects. We also observed increased H(2)S levels in HF subjects following 400 mg SG1002. Nitrite, a metabolite of NO, was increased in both healthy and HF patients receiving 400 mg and 800 mg SG1002. HF subjects treated with SG1002 displayed stable drug levels over the course of the trial. SG1002 was safe and well tolerated at all doses in both healthy and HF subjects. These data suggest that SG1002 increases blood H(2)S levels and circulating NO bioavailability. The finding that SG1002 attenuates increases in BNP in HF patients suggests that this novel agent warrants further study in a larger clinical study.
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spelling pubmed-50348032016-10-03 A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients Polhemus, David J. Li, Zhen Pattillo, Christopher B. Gojon, Gabriel Gojon, Gabriel Giordano, Tony Krum, Henry Cardiovasc Ther Expedited Recent studies demonstrate robust molecular cross talk and signaling between hydrogen sulfide (H(2)S) and nitric oxide (NO). Heart failure (HF) patients are deficient in both H(2)S and NO, two molecules that are critical for cardiovascular homeostasis. A phase I clinical trial of a novel H(2)S prodrug (SG1002) was designed to assess safety and changes in H(2)S and NO bioavailability in healthy and HF subjects. Healthy subjects (n = 7) and heart failure patients (n = 8) received oral SG1002 treatment in escalating dosages of 200, 400, and 800 mg twice daily for 7 days for each dose. Safety and tolerability were assessed by physical examination, vital signs, and ECG analysis. Plasma samples were collected during a 24‐h period each week for H(2)S and NO analysis. BNP and glutathione levels were analyzed as markers of cardiac health and redox status. Administration of SG1002 resulted in increased H(2)S levels in healthy subjects. We also observed increased H(2)S levels in HF subjects following 400 mg SG1002. Nitrite, a metabolite of NO, was increased in both healthy and HF patients receiving 400 mg and 800 mg SG1002. HF subjects treated with SG1002 displayed stable drug levels over the course of the trial. SG1002 was safe and well tolerated at all doses in both healthy and HF subjects. These data suggest that SG1002 increases blood H(2)S levels and circulating NO bioavailability. The finding that SG1002 attenuates increases in BNP in HF patients suggests that this novel agent warrants further study in a larger clinical study. John Wiley and Sons Inc. 2015-07-07 2015-08 /pmc/articles/PMC5034803/ /pubmed/25930144 http://dx.doi.org/10.1111/1755-5922.12128 Text en © 2015 SulfaGENIX Inc. Cardiovascular Therapeutics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Expedited
Polhemus, David J.
Li, Zhen
Pattillo, Christopher B.
Gojon, Gabriel
Gojon, Gabriel
Giordano, Tony
Krum, Henry
A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients
title A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients
title_full A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients
title_fullStr A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients
title_full_unstemmed A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients
title_short A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients
title_sort novel hydrogen sulfide prodrug, sg1002, promotes hydrogen sulfide and nitric oxide bioavailability in heart failure patients
topic Expedited
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034803/
https://www.ncbi.nlm.nih.gov/pubmed/25930144
http://dx.doi.org/10.1111/1755-5922.12128
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