Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Chad D. Schwartzkopf, John R. Hadcock, Guang Liu, Peter Germano, Julien Roux, Courtney M. Shea, Emmanuel S. Buys, Juli E. Jones
Summary: Praliciguat treatment showed metabolic effects of increasing energy utilization, improving insulin sensitivity, and reducing plasma triglycerides in diet-induced obesity (DIO) mice.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Alexandra Petraina, Cristian Nogales, Thomas Krahn, Hermann Mucke, Thomas F. Luscher, Rodolphe Fischmeister, David A. Kass, John C. Burnett, Adrian J. Hobbs, Harald H. H. W. Schmidt
Summary: Mechanism-based therapy focused on understanding disease pathways at the molecular level is still rare in cardiovascular medicine, but recent drug developments centered around cGMP offer promising personalized treatment options. By modulating cGMP synthesis or breakdown, these drugs show potential for protective effects across various cardiac conditions.
CARDIOVASCULAR RESEARCH
(2022)
Review
Medicine, Research & Experimental
Juan Xia, Nan Hui, Lei Tian, Chengyuan Liang, Jie Zhang, Jifang Liu, Jun Wang, Xiaodong Ren, Xiaolin Xie, Kun Wang
Summary: Vericiguat is the first approved drug for reducing symptoms in chronic HF patients, reducing the occurrence of HF worsening. This article provides comprehensive information about Vericiguat and insights into current HF treatments.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Francesca Vannuccini, Alessandro Campora, Maria Barilli, Alberto Palazzuoli
Summary: Vericiguat is a drug that aims to restore signaling pathway deficiency in heart failure and reduce oxidative stress and endothelial dysfunction. Clinical trials have shown its effectiveness in reducing event rates in heart failure patients with reduced ejection fraction, but its benefits in patients with preserved ejection fraction are limited.
Article
Cardiac & Cardiovascular Systems
Douglas L. Mann, G. Michael Felker
Summary: Despite numerous attempts to develop a unifying hypothesis explaining HFrEF pathophysiology, no single conceptual model has proven to be enduring. This review discusses how recent successful clinical development programs for HFrEF build upon existing conceptual models and identifies areas where further refinement may be needed. Analysis of four new therapeutic drug classes, including ARNIs, SGLT2 inhibitors, soluble guanylate cyclase stimulators, and myosin activators, indicates significant advances based on existing conceptual models, with SGLT2 inhibitors potentially representing a major recent breakthrough in cardiovascular therapeutics.
CIRCULATION RESEARCH
(2021)
Article
Neurosciences
Neil M. Otto, Lincoln R. Potter
Summary: Multisite phosphorylation is required for receptor activation of GC-A, and vicinal glutamate substitutions are better phosphomimetics. Phosphorylation is crucial for the allosteric activation of GC-A.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Xiao-Yan Jia, Yong-Ming Liu, Yong-Fei Wang, Jin-Yang An, Ke-Ling Peng, Hua Wang
Summary: This study examined the trends and hotspots in cardiovascular research on soluble guanylate cyclase (sGC) stimulators by analyzing publications retrieved from the Web of Science Core Collection. The results showed a gradual increase in the overall volume of publications in this field. The study also identified the leading driving force, top authors, and main research hotspots in CV research on sGC stimulators. The findings suggested that the treatment of heart failure, especially heart failure with preserved ejection fraction, may be the current and future research focus in this area.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
David S. Weinberg, Nathan R. Foster, Gary Della'Zanna, Ryan P. McMurray, Walter K. Kraft, Angela Pallotto, David M. Kastenberg, Leo C. Katz, Christopher H. Henry, Stephanie M. Moleski, Paul J. Limburg, Scott A. Waldman
Summary: Studies suggest that oral GUCY2C agonist could be an effective chemoprevention agent for colorectal cancer, but the investigational oral uroguanylin analog dolcanatide did not activate GUCY2C in epithelial cells of the distal rectum in healthy volunteers, indicating its enhanced stability and extended persistence may not be sufficient to regulate GUCY2C across the colorectum for tumor prevention.
CANCER BIOLOGY & THERAPY
(2021)
Review
Cardiac & Cardiovascular Systems
Alberto Aimo, Vincenzo Castiglione, Giuseppe Vergaro, Giorgia Panichella, Michele Senni, Carlo Mario Lombardi, Michele Emdin
Summary: Heart failure with reduced or preserved ejection fraction is associated with significant morbidity and mortality, warranting the search for novel therapeutic agents. The nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway is disrupted in heart failure, and sGC activators or stimulators may be effective in treating this condition. Vericiguat has shown safety and efficacy in patients with HFrEF, but caution is needed in its use.
HEART FAILURE REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Anna Avesani, Laura Bielefeld, Nicole Weisschuh, Valerio Marino, Pascale Mazzola, Katarina Stingl, Tobias B. Haack, Karl-Wilhelm Koch, Daniele Dell'Orco
Summary: This study characterizes the biochemical and biophysical properties of human GCAP3 and identifies a mutation in GUCA1C that may contribute to retinitis pigmentosa.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Masashi Tawa, Takashi Shimosato, Keisuke Nakagawa, Tomio Okamura, Mamoru Ohkita
Summary: This study found that renovascular hypertension did not affect the vasorelaxant responses mediated by NO-sensitive and NO-insensitive forms of sGC, suggesting that sGC may not be responsible for the reduced NO bioavailability observed during renovascular hypertension.
Article
Cardiac & Cardiovascular Systems
Theresa-Marie Dachs, Franz Duca, Rene Rettl, Christina Binder-Rodriguez, Daniel Dalos, Luciana Camuz Ligios, Andreas Kammerlander, Ekkehard Grunig, Ingrid Pretsch, Regina Steringer-Mascherbauer, Klemens Ablasser, Manfred Wargenau, Julia Mascherbauer, Irene M. Lang, Christian Hengstenberg, Roza Badr-Eslam, Johannes Kastner, Diana Bonderman
Summary: This study investigated the efficacy of riociguat, an oral soluble guanylate cyclase stimulator, in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). The results showed that riociguat improved hemodynamics in PH-HFpEF but did not change clinical symptoms within the study period. There were some adverse events associated with riociguat, leading to more dropouts compared to placebo.
EUROPEAN HEART JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Michael Boettcher, Stephanie Loewen, Mireille Gerrits, Corina Becker
Summary: Vericiguat, when coadministered with drugs commonly used for heart failure or with narrow therapeutic index like warfarin, demonstrated good safety and tolerability with no clinically relevant pharmacodynamic or pharmacokinetic interactions, supporting their concomitant use without dose adjustment.
CLINICAL PHARMACOKINETICS
(2021)
Article
Biochemistry & Molecular Biology
Ellis Nelissen, Elentina K. Argyrousi, Nick P. Van Goethem, Fuqiang Zhao, Catherine D. G. Hines, Gayathri Swaminath, Michael Gerisch, Joerg Hueser, Peter Sandner, Jos Prickaerts
Summary: The study found that the sGC stimulator vericiguat can enhance long-term memory by increasing hippocampal plasticity and promoting the translocation of oc-AMPA receptors to the cell membrane, while having no effect on blood pressure and cerebral blood volume. Stimulation of sGC may provide a new therapeutic strategy for treating VCI.