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).

Author affiliations

1. Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, CLN 309, Boston, Massachusetts 02114, USA.
2. Department of Surgery, Tufts-New England Medical Center, Tufts University School of Medicine, 750 Washington Street, NEMC #154, Boston, Massachusetts 02111, USA.
3. Section on Oxidative Stress and Tissue Injury, Laboratory of Physiological Studies, National Institutes of Health/NIAAA, 5625 Fishers Lane, Room 2N-17, Bethesda, Maryland 20892, USA.
4. Department of Pharmacology, School of Biomedical Sciences, Monash University, Wellington Road, Melbourne, Victoria 3800, Australia.
5. Center for Vascular Health, Monash University, Melbourne, Victoria 3800, Australia.
6. Department of Surgery, University of Medicine and Dentistry-New Jersey Medical School, 185 South Orange Avenue, University Heights, Newark, New Jersey 07103, USA.
7. Institute of Cardiovascular Research, Bayer HealthCare AG, Aprather Weg 18a, Wuppertal D-42096, Germany.

Correspondence to: Oleg V. Evgenov^1,2 Email: evgenov@etherdome.mgh.harvard.edu

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