Volume 14 Supplement 1

6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access

Targeting native and apo-sGC

  • Mary Struthers1Email author,
  • Subharekha Raghavan1,
  • Ronald Kim1,
  • Christopher Sinz1,
  • Sophie Roy1 and
  • Michael Mendelsohn1
BMC Pharmacology and Toxicology201314(Suppl 1):O17

DOI: 10.1186/2050-6511-14-S1-O17

Published: 29 August 2013

Soluble guanylate cyclase (sGC), the receptor for nitric oxide (NO), is one component of the nitric oxide (NO)-sGC-cGMP signaling pathway, which plays a key role in the cardiovascular system regulating smooth muscle relaxation and vasodilation and has been implicated in remodeling events in the heart and vasculature. Triggered by the binding endothelial-derived NO to the prosthetic heme group, sGC in smooth muscle cells converts GTP to the secondary messenger cGMP. Small molecule activators of sGC have been identified that either have the ability to activate the native heme-containing form of the enzyme (Heme-Dependent activators) or have the ability to activate to heme-free or oxidized form of the enzyme (Heme-Independent activators). The therapeutic potential of activators of sGC is illustrated by the successful clinical evaluation by Bayer of a Heme-dependent activator riociguat in pulmonary arterial hypertension [1]. The characterization of both heme-dependent and heme-independent activators with regard to their biochemical interactions with the enzyme as well as preclinical in vivo activity in rodent models of systemic and pulmonary hypertension will be presented.

Authors’ Affiliations

(1)
Merck Research Laboratories

References

  1. Ghofrani HA, Hoeper MM, Halank M, Meyer FJ, Staehler G, Behr J, Ewert R, Weimann G, Grimminger F: Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Res J. 2010, 36: 792-799. 10.1183/09031936.00182909.View ArticleGoogle Scholar

Copyright

© Struthers et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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