Email updates

Keep up to date with the latest news and content from BMC Pharmacology and BioMed Central.

This article is part of the supplement: 5th International Conference on cGMP: Generators, Effectors and Therapeutic Implications

Open Access Open Badges Oral presentation

Structural insights into sGC activation by different activators

Focco van den Akker1*, Faye Martin1, Vijay Kumar1, Xiaolei Ma1, Johannes-Peter Stasch2, Martina Schaefer2, Padmamalini Baskaran3, Annie Beuve3 and Pete W van Dunten4

Author Affiliations

1 Department of Biochemistry/RT500, Case Western Reserve University, Cleveland, OH 44106, USA

2 Cardiovascular Research, Bayer Schering Pharma AG, Wuppertal D-42096, Germany

3 Department of Pharmacology and Physiology, New Jersey Medical School, U. Of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA

4 Stanford Synchrotron Radiation Laboratory, Stanford University, Menlo Park, CA 94025, USA

For all author emails, please log on.

BMC Pharmacology 2011, 11(Suppl 1):O11  doi:10.1186/1471-2210-11-S1-O11

The electronic version of this article is the complete one and can be found online at:

Published:1 August 2011

© 2011 van den Akker et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The soluble guanylyl cyclase (sGC) is a key enzyme involved in the production of the second messenger cGMP. Due its cardiovascular relevance, sGC has been the target of numerous drug discovery efforts leading to the development of many different activators and stimulators with pharmaceutical potential. One of such compounds is the sGC activator Cinaciguat (BAY 58-2667) which is in clinical trials for acute decompensated heart failure.


We present here our latest structure-function studies related to sGC activation by different sGC activators. The activator complex structures reveal an intriguing mode of heme mimicry by these compounds. The observed activation conformational changes center around the αF helix that contains the H105 residue normally held in place by the heme moiety in the absence of the activators.


The structural insights gained from the complex structures could be used for further optimization and development of sGC activators.