Article
Medicine, General & Internal
John R. Teerlink, Rafael Diaz, G. Michael Felker, John J. V. McMurray, Marco Metra, Scott D. Solomon, Kirkwood F. Adams, Inder Anand, Alexandra Arias-Mendoza, Tor Biering-Sorensen, Michael Bohm, Diana Bonderman, John G. F. Cleland, Ramon Corbalan, Maria G. Crespo-Leiro, Ulf Dahlstrom, Luis E. Echeverria, James C. Fang, Gerasimos Filippatos, Candida Fonseca, Eva Goncalvesova, Assen R. Goudev, Jonathan G. Howlett, David E. Lanfear, Jing Li, Mayanna Lund, Peter Macdonald, Viacheslav Mareev, Shin-ichi Momomura, Eileen O'Meara, Alexander Parkhomenko, Piotr Ponikowski, Felix J. A. Ramires, Pranas Serpytis, Karen Sliwa, Jindrich Spinar, Thomas M. Suter, Janos Tomcsanyi, Hans Vandekerckhove, Dragos Vinereanu, Adriaan A. Voors, Mehmet B. Yilmaz, Faiez Zannad, Lucie Sharpsten, Jason C. Legg, Claire Varin, Narimon Honarpour, Siddique A. Abbasi, Fady I. Malik, Christopher E. Kurtz
Summary: Among patients with heart failure and reduced ejection fraction, those who received omecamtiv mecarbil had a lower incidence of heart-failure events or cardiovascular death compared to those who received placebo over a median of 22 months.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Chemistry, Physical
Ananya Chakraborti, Jil C. Tardiff, Steven D. Schwartz
Summary: The study investigated the influence of the positive inotrope Omecamtiv mecarbil (OM) on the recovery stroke of cardiac myosin, as well as its effects in the presence of genetic cardiomyopathic mutations. The study utilized metadynamics and transition path sampling to gain insights into the dynamics and mechanism of ATP hydrolysis in the presence of OM. Understanding the effects of OM is crucial for its potential use in the treatment of cardiac disease.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Pharmacology & Pharmacy
Ashit Trivedi, Cheng-Pang Hsu, Pegah Jafarinasabian, Bianca Terminello, Hanze Zhang, Stephen Flach, Samuel Israel, Ashley Brooks, Hongqi Xue, Borje Darpo, Siddique Abbasi, Sandeep Dutta, Edward Lee
Summary: The study found that Omecamtiv mecarbil (OM) at therapeutic concentrations has no clinically relevant effect on ECG parameters and does not affect the QTc interval significantly up to a plasma concentration of approximately 800 ng/mL. No serious adverse events leading to discontinuation from the study were observed.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Monika Halas, Paulina Langa, Chad M. Warren, Paul H. Goldspink, Beata M. Wolska, R. John Solaro
Summary: The study investigated the effects of OM and Mava on different isoforms of sarcomeres in developing cardiac myocytes. OM increased Ca2+-sensitivity and decreased cooperative activation, while Mava reduced tension in mature myofilaments.
MOLECULAR PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Scott D. Solomon, Brian L. Claggett, Zi Michael Miao, Rafael Diaz, G. Michael Felker, John J. McMurray, Marco Metra, Ramon Corbalan, Gerasimos Filippatos, Assen R. Goudev, Viatcheslav Mareev, Pranas Serpytis, Thomas Suter, Mehmet B. Yilmaz, Faiez Zannad, Stuart Kupfer, Stephen B. Heitner, Fady Malik, John R. Teerlink
Summary: In the GALACTIC-HF study, the influence of atrial fibrillation on the effectiveness of omecamtiv mecarbil was explored. The study found that patients with atrial fibrillation derived less benefit from omecamtiv mecarbil treatment, especially those who were also receiving digoxin.
EUROPEAN HEART JOURNAL
(2022)
Article
Physiology
Tomohiro Nakanishi, Kotaro Oyama, Hiroyuki Tanaka, Fuyu Kobirumaki-Shimozawa, Shuya Ishii, Takako Terui, Shin'ichi Ishiwata, Norio Fukuda
Summary: The novel inotropic agent Omecamtiv mecarbil increases the sensitivity of cardiac muscle to calcium, leading to enhanced contractile properties. However, this effect is attenuated under the influence of fast skeletal troponin and strongly bound cross-bridges, suggesting a complex regulatory mechanism for its positive inotropic effects.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Arnold Peter Raduly, Attila Toth, Fruzsina Sarkany, Balazs Horvath, Norbert Szentandrassy, Peter P. Nanasi, Zoltan Csanadi, Istvan Edes, Zoltan Papp, Attila Borbely
Summary: This study aimed to compare the effects of different mechanisms of calcium-sensitizing positive inotropic agents (OM, EMD, and Levo) on cardiomyocytes. The results showed that OM exerted its positive inotropic effect by prolonging systolic contraction and increasing calcium sensitivity. In contrast, EMD and Levo exerted positive inotropic effects through different mechanisms. These findings have important implications for the further development of drugs for treating heart failure.
Article
Medicine, General & Internal
Gregory D. Lewis, Adriaan A. Voors, Alain Cohen-Solal, Marco Metra, David J. Whellan, Justin A. Ezekowitz, Michael Bohm, John R. Teerlink, Kieran F. Docherty, Renato D. Lopes, Punag H. Divanji, Stephen B. Heitner, Stuart Kupfer, Fady Malik, Lisa Meng, Amy Wohltman, G. Michael Felker
Summary: In patients with chronic HFrEF, omecamtiv mecarbil did not significantly improve exercise capacity over 20 weeks compared with placebo.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Article
Multidisciplinary Sciences
Shih-Ni Wu, Min-Shan Tsai, Chien-Hua Huang, Wen-Jone Chen
Summary: OM treatment improves post-resuscitation myocardial dysfunction and neurological outcome, supporting further pre-clinical studies to enhance post-cardiac arrest care.
Article
Biology
Aaron Snoberger, Bipasha Barua, Jennifer L. Atherton, Henry Shuman, Eva Forgacs, Yale E. Goldman, Donald A. Winkelmann, E. Michael Ostap
Summary: The study revealed a novel mechanism, showing that the R712L mutation decreases the working stroke of myosin, while OM is able to rescue this inhibition, providing insights into the pathogenesis of HCM.
Article
Cardiac & Cardiovascular Systems
Alexandra Rhoden, Thomas Schulze, Niels Pietsch, Torsten Christ, Arne Hansen, Thomas Eschenhagen
Summary: The study found that the effects of OM on contractility and diastolic tension are complex and influenced by concentration, time, species, and loading conditions. Further research is needed to explore the effects on mitochondrial function.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chih-Yu Ting, Chia-Lung Shih, Meng-Cheng Yu, Chao-Liang Wu, Sheng-Nan Wu
Summary: Omecamtiv mecarbil (OM, CK-1827452) is an activator of myosin and has been shown to be beneficial for the treatment of systolic heart failure. However, its effects on ionic currents in electrically excitable cells are not well understood. This study investigated the effects of OM on ionic currents in GH3 pituitary cells and Neuro-2a neuroblastoma cells.
Article
Pharmacology & Pharmacy
Ashit Trivedi, Mia Mackowski, Pegah Jafarinasabian, Hanze Zhang, Stephen Flach, Bianca Terminello, Ajay Bhatia, Sandeep Dutta, Edward Lee
Summary: The study aimed to determine the bioavailability of two OM minitablet formulations relative to the adult matrix MR formulation. Results showed that the slow-release and fast-release minitablets demonstrated bioavailability similar to the adult matrix MR formulation.
CLINICAL DRUG INVESTIGATION
(2021)
Article
Physiology
Ranganath Mamidi, Joshua B. Holmes, Chang Yoon Doh, Katherine L. Dominic, Nikhil Madugula, Julian E. Stelzer
Summary: This study investigated the effects of OM on force generation and cross-bridge kinetics in myocardial preparations with reduced cMyBPC phosphorylation. The results showed significant differences in the effects of OM between WT and SA myocardial preparations, suggesting an interplay between OM and XB behavior which may alter the cardiac response to 13-adrenergic stimulation.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Yusheng Qu, BaoXi Gao, Ziva Arimura, Mei Fang, Hugo M. Vargas
Summary: Omecamtiv mecarbil (OM) is a myosin activator developed for treating heart failure. Studies showed that OM had minimal impact on the heart in a series of experiments, indicating no delay in ventricular repolarization.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Tamas Csipo, Agnes Czikora, Gabor A. Fulop, Hajnalka Gulyas, Ibolya Rutkai, Eniko Pasztorne Toth, Robert Porszasz, Andrea Szalai, Kata Bolcskei, Zsuzsanna Helyes, Erika Pinter, Zoltan Papp, Zoltan Ungvari, Attila Toth
Summary: TRPM4 plays a significant role in peripheral arteries by amplifying intracellular Ca2+ signals, contributing to myogenic tone and agonist responses. It may have important implications for circulation and hypertension.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Arnold Peter Raduly, Fruzsina Sarkany, Mate Balazs Kovacs, Brigitta Bernat, Bela Juhasz, Zoltan Szilvassy, Robert Porszasz, Balazs Horvath, Norbert Szentandrassy, Peter Nanasi, Zoltan Csanadi, Istvan Edes, Attila Toth, Zoltan Papp, Daniel Priksz, Attila Borbely
Summary: Recent cardiotropic drug developments have focused on cardiac myofilaments, and danicamtiv, as the second direct myosin activator, has shown promising results in the treatment of heart failure with reduced ejection fraction. In vitro and in vivo studies have demonstrated that danicamtiv improves systolic function but may also limit diastolic performance at higher concentrations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Piero Pollesello, Zoltan Papp
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Arnold Peter Raduly, Attila Toth, Fruzsina Sarkany, Balazs Horvath, Norbert Szentandrassy, Peter P. Nanasi, Zoltan Csanadi, Istvan Edes, Zoltan Papp, Attila Borbely
Summary: This study aimed to compare the effects of different mechanisms of calcium-sensitizing positive inotropic agents (OM, EMD, and Levo) on cardiomyocytes. The results showed that OM exerted its positive inotropic effect by prolonging systolic contraction and increasing calcium sensitivity. In contrast, EMD and Levo exerted positive inotropic effects through different mechanisms. These findings have important implications for the further development of drugs for treating heart failure.
Article
Biochemistry & Molecular Biology
Alexander J. Kozuch, Pavel A. Petukhov, Miklos Fagyas, Isolda A. Popova, Matthew O. Lindeblad, Alexander P. Bobkov, Armais A. Kamalov, Attila Toth, Steven M. Dudek, Sergei M. Danilov
Summary: Urinary ACE activity/levels are lower than in the blood and may be associated with renal tubular damage. ACE phenotyping in urine revealed sex-dependent differences in ACE immunoreactivity and potential utility as a feedback marker for weight loss. This novel approach has promising clinical significance for precision medicine screening.
Article
Chemistry, Medicinal
Brigitta Bernat, Rita Erdelyi, Laszlo Fazekas, Greta Garami, Reka Maria Szekeres, Barbara Takacs, Mariann Bombicz, Balazs Varga, Fruzsina Sarkany, Arnold Peter Raduly, Dana Diana Romanescu, Zoltan Papp, Attila Toth, Zoltan Szilvassy, Bela Juhasz, Daniel Priksz
Summary: Multi-target drug candidate BGP-15 has demonstrated cardioprotective and antiarrhythmic effects in diseased models. This study investigated the effects of BGP-15 on ECG and echocardiographic parameters, heart rate variability (HRV), and arrhythmia incidence. The results showed that BGP-15 did not affect the ECG waveforms, but decreased heart rate and increased vagally mediated HRV, while reducing arrhythmogenesis and improving left ventricle relaxation.
Article
Chemistry, Medicinal
Zsigmond Mate Kovacs, Jozsef Ovari, Csaba Dienes, Janos Magyar, Tamas Banyasz, Peter P. Nanasi, Balazs Horvath, Adam Feher, Zoltan Varga, Norbert Szentandrassy
Summary: ABT-333, an antiviral agent used in hepatitis C treatment, may pose a risk of arrhythmia due to its methanesulfonamide group. It was found that ABT-333 can reduce ion currents and action potentials in myocardial cells, leading to an increase in early plateau potential and occurrence of abnormal action potentials in some cells. However, considering its therapeutic plasma concentration, the risk of arrhythmia with ABT-333 is very low even in case of drug overdose.
Article
Chemistry, Medicinal
Balazs Horvath, Zsigmond Kovacs, Csaba Dienes, Jozsef Ovari, Norbert Szentandrassy, Janos Magyar, Tamas Banyasz, Andras Varro, Peter P. Nanasi
Summary: The characteristics of late sodium current (I-Na,I-late) and its conductance changes (G(Na,late)) were studied in rabbit, canine, and guinea pig ventricular myocytes. The gating kinetics of I-Na,I-late showed notable interspecies differences, which cannot be explained by differences in action potential morphology. Intracellular Ca2+ concentration and Anemonia sulcata (ATX-II) toxin also influenced the I-Na,I-late and G(Na,late) profiles differently in canine and guinea pig myocytes.