NO-independent stimulators and activators of soluble guanylate cyclase: Discovery and therapeutic potential

Oleg V. Evgenov, Pál Pacher, Peter M. Schmidt, György Haskó, Harald H H W Schmidt, Johannes Peter Stasch

Research output: Contribution to journalArticle

476 Citations (Scopus)

Abstract

Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impaired bioavailability and/or responsiveness to endogenous NO has been implicated in the pathogenesis of cardiovascular and other diseases. Current therapies that involve the use of organic nitrates and other NO donors have limitations, including non-specific interactions of NO with various biomolecules, lack of response and the development of tolerance following prolonged administration. Compounds that activate sGC in an NO-independent manner might therefore provide considerable therapeutic advantages. Here we review the discovery, biochemistry, pharmacology and clinical potential of haem-dependent sGC stimulators (including YC-1, BAY 41-2272, BAY 41-8543, CFM-1571 and A-350619) and haem-independent sGC activators (including BAY 58-2667 and HMR-1766).

Original languageEnglish
Pages (from-to)755-768
Number of pages14
JournalNature Reviews Drug Discovery
Volume5
Issue number9
DOIs
Publication statusPublished - Sep 2006

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Nitric Oxide
3-(2-(4-chlorophenylsulfanyl)phenyl)-N-(4-dimethylaminobutyl)acrylamide
Heme
Nitric Oxide Donors
Clinical Pharmacology
Therapeutics
Biochemistry
Nitrates
Biological Availability
Signal Transduction
Cardiovascular Diseases
Soluble Guanylyl Cyclase
Enzymes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

NO-independent stimulators and activators of soluble guanylate cyclase : Discovery and therapeutic potential. / Evgenov, Oleg V.; Pacher, Pál; Schmidt, Peter M.; Haskó, György; Schmidt, Harald H H W; Stasch, Johannes Peter.

In: Nature Reviews Drug Discovery, Vol. 5, No. 9, 09.2006, p. 755-768.

Research output: Contribution to journalArticle

Evgenov, Oleg V. ; Pacher, Pál ; Schmidt, Peter M. ; Haskó, György ; Schmidt, Harald H H W ; Stasch, Johannes Peter. / NO-independent stimulators and activators of soluble guanylate cyclase : Discovery and therapeutic potential. In: Nature Reviews Drug Discovery. 2006 ; Vol. 5, No. 9. pp. 755-768.
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