ArticleBritish journal of pharmacology2002
NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle.
Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 310 citations in OpenAlex.
- NO modulates human airway smooth muscle function by altering glucose-6-phosphate dehydrogenase effects on sGC function in asthma.Redox biology · 2026Article
- Beta arrestin 1 is a key regulator of pulmonary vascular tone.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pathophysiology of Pulmonary Arterial Hypertension: Focus on Vascular Endothelium as a Potential Therapeutic Target.International journal of molecular sciences · 2025Review
- Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Sex-dependent adaptations in heart mitochondria from transgenic mice overexpressing cytochrome bMitochondrion · 2025Article
- New therapies in pulmonary arterial hypertension: Recent insights.International journal of cardiology. Congenital heart disease · 2025Article
- Stimulating Soluble Guanylyl Cyclase with the Clinical Agonist Riociguat Restrains the Development and Progression of Castration-Resistant Prostate Cancer.Cancer research · 2025Article
- Mechanisms Underlying the Effects of Chloroquine on Red Blood Cells Metabolism.International journal of molecular sciences · 2024Article
- NO-ferroheme is a signaling entity in the vasculature.Nature chemical biology · 2023Article
- Methylene Blue Inhibits Cromakalim-Activated KMembranes · 2023Article
- Dental Pulp Inflammation Initiates the Occurrence of Mast Cells Expressing the αInternational journal of molecular sciences · 2023Article
- Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive diseases.Frontiers in pharmacology · 2023Review
- Inhaled mosliciguat (BAY 1237592): targeting pulmonary vasculature via activating apo-sGC.Respiratory research · 2022Article
- Soluble guanylate cyclase activator BAY 54-6544 improves vasomotor function and survival in an accelerated ageing mouse model.Aging cell · 2022Article
- The role of activation of two different sGC binding sites by NO-dependent and NO-independent mechanisms in the regulation of SACs in rat ventricular cardiomyocytes.Physiological reports · 2022Article
- Smooth muscle cell CYB5R3 preserves cardiac and vascular function under chronic hypoxic stress.Journal of molecular and cellular cardiology · 2022Article
- Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino.Frontiers in physiology · 2022Article
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
- Contemporary Pillars of Heart Failure with Reduced Ejection Fraction Medical Therapy.Journal of clinical medicine · 2021Review
- Activation mechanism of human soluble guanylate cyclase by stimulators and activators.Nature communications · 2021Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. Soluble guanylyl cyclase (sGC) is the only proven receptor for the ubiquitous biological messenger nitric oxide (NO) and is intimately involved in many signal transduction pathways, most notably in regulating vascular tone and platelet function. sGC is a heterodimeric (alpha/ss) protein that converts GTP to cyclic GMP; NO binds to its prosthetic haem group. Here, we report the discovery of a novel sGC activating compound, its interaction with a previously unrecognized regulatory site and its therapeutic implications. 2. Through a high-throughput screen we identified BAY 58-2667, an amino dicarboxylic acid which potently activates sGC in an NO-independent manner. In contrast to NO, YC-1 and BAY 41-2272, the sGC stimulators described recently, BAY 58-2667 activates the enzyme even after it has been oxidized by the sGC inhibitor ODQ or rendered haem deficient. 3. Binding studies with radiolabelled BAY 58-2667 show a high affinity site on the enzyme. 4. Using photoaffinity labelling studies we identified the amino acids 371 (alpha-subunit) and 231 - 310 (ss-subunit) as target regions for BAY 58-2667. 5. sGC activation by BAY 58-2667 results in an antiplatelet activity both in vitro and in vivo and a potent vasorelaxation which is not influenced by nitrate tolerance. 6. BAY 58-2667 shows a potent antihypertensive effect in conscious spontaneously hypertensive rats. In anaesthetized dogs the hemodynamic effects of BAY 58-2667 and GTN are very similar on the arterial and venous system. 7. This novel type of sGC activator is a valuable research tool and may offer a new approach for treating cardiovascular diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.