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Ularitide for the treatment of acute decompensated heart failure: from preclinical to clinical studies.

Anker SD, Ponikowski P, Mitrovic V, Peacock WF, Filippatos G - Eur. Heart J. (2015)

Bottom Line: There is an unmet need for new therapy options with new drugs with a new mode of action.One of the drugs currently in clinical testing in Phase III is ularitide, which is the chemically synthesized form of the human natriuretic peptide urodilatin.In animal models of heart failure as well as Phase I and II clinical studies in heart failure patients, ularitide demonstrated beneficial effects such as symptom relief and vasodilation, while still preserving renal function.

View Article: PubMed Central - PubMed

Affiliation: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany s.anker@cachexia.de.

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Related in: MedlinePlus

Schematic drawing of the role of urodilatin under physiological and pathophysiological conditions. (A) Nephron highlighting distal tubule (synthesis site of urodilatin) and collecting duct (binding site of urodilatin). (B) sodium concentration as stimulus for synthesis of urodilatin in distal tubule cells and excretion into the urine, mediated by transduction mechanisms:19 AC, adenylyl cyclyse; PKC, protein kinase (C) and binding to NPR-A receptor in the inner medullary collecting duct. (C) Processing of urodilatin from pro-ANP. Enzyme responsible not known yet (aa, amino acids).
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EHU484F1: Schematic drawing of the role of urodilatin under physiological and pathophysiological conditions. (A) Nephron highlighting distal tubule (synthesis site of urodilatin) and collecting duct (binding site of urodilatin). (B) sodium concentration as stimulus for synthesis of urodilatin in distal tubule cells and excretion into the urine, mediated by transduction mechanisms:19 AC, adenylyl cyclyse; PKC, protein kinase (C) and binding to NPR-A receptor in the inner medullary collecting duct. (C) Processing of urodilatin from pro-ANP. Enzyme responsible not known yet (aa, amino acids).

Mentions: Ularitide is the chemically synthesized form of urodilatin, a human natriuretic peptide, produced by differential processing of pro-atrial natriuretic peptide in distal renal tubule cells.1,2 It is a 32-amino acid-containing peptide with the same structure as the 28-amino acid-containing atrial natriuretic peptide (ANP), except for the addition of four amino acids at the N-terminal extension.3 Urodilatin is secreted into urine and forms the basis for a paracrine system regulating water and sodium reabsorption at the level of the collecting duct (Figure 1).1,4 Urodilatin was first isolated from human urine by Wolf-Georg Forssmann's group in 1988.3Figure 1


Ularitide for the treatment of acute decompensated heart failure: from preclinical to clinical studies.

Anker SD, Ponikowski P, Mitrovic V, Peacock WF, Filippatos G - Eur. Heart J. (2015)

Schematic drawing of the role of urodilatin under physiological and pathophysiological conditions. (A) Nephron highlighting distal tubule (synthesis site of urodilatin) and collecting duct (binding site of urodilatin). (B) sodium concentration as stimulus for synthesis of urodilatin in distal tubule cells and excretion into the urine, mediated by transduction mechanisms:19 AC, adenylyl cyclyse; PKC, protein kinase (C) and binding to NPR-A receptor in the inner medullary collecting duct. (C) Processing of urodilatin from pro-ANP. Enzyme responsible not known yet (aa, amino acids).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368857&req=5

EHU484F1: Schematic drawing of the role of urodilatin under physiological and pathophysiological conditions. (A) Nephron highlighting distal tubule (synthesis site of urodilatin) and collecting duct (binding site of urodilatin). (B) sodium concentration as stimulus for synthesis of urodilatin in distal tubule cells and excretion into the urine, mediated by transduction mechanisms:19 AC, adenylyl cyclyse; PKC, protein kinase (C) and binding to NPR-A receptor in the inner medullary collecting duct. (C) Processing of urodilatin from pro-ANP. Enzyme responsible not known yet (aa, amino acids).
Mentions: Ularitide is the chemically synthesized form of urodilatin, a human natriuretic peptide, produced by differential processing of pro-atrial natriuretic peptide in distal renal tubule cells.1,2 It is a 32-amino acid-containing peptide with the same structure as the 28-amino acid-containing atrial natriuretic peptide (ANP), except for the addition of four amino acids at the N-terminal extension.3 Urodilatin is secreted into urine and forms the basis for a paracrine system regulating water and sodium reabsorption at the level of the collecting duct (Figure 1).1,4 Urodilatin was first isolated from human urine by Wolf-Georg Forssmann's group in 1988.3Figure 1

Bottom Line: There is an unmet need for new therapy options with new drugs with a new mode of action.One of the drugs currently in clinical testing in Phase III is ularitide, which is the chemically synthesized form of the human natriuretic peptide urodilatin.In animal models of heart failure as well as Phase I and II clinical studies in heart failure patients, ularitide demonstrated beneficial effects such as symptom relief and vasodilation, while still preserving renal function.

View Article: PubMed Central - PubMed

Affiliation: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany s.anker@cachexia.de.

Show MeSH
Related in: MedlinePlus