Cardiac myosin activator. Medical search. Frequent questions

Omecamtiv mecarbil is a novel cardiac myosin activator, a cardiac myotrope, that has demonstrated to improve cardiac remodeling and systolic function of the heart and decrease heart rate and NT-proBNP levels in patients with HFrEF. (pace-cme.org)
The Global Approach To Lowering Adverse Cardiac Outcomes Through Improving Contractility In Heart Failure (GALACTIC-HF) trial tested whether omecamtiv mecarbil improved clinical outcomes in HFrEF patients compared to placebo. (pace-cme.org)
Omecamtiv mecarbil (INN), previously referred to as CK-1827452, is a cardiac-specific myosin activator. (wikipedia.org)
Furthermore, once myosin is bound to actin, it stays bound dramatically longer in the presence of omecamtiv mecarbil. (wikipedia.org)
Thus omecamtiv mecarbil improves systolic function by increasing the systolic ejection duration and stroke volume, without consuming more ATP energy, oxygen or altering intracellular calcium levels causing an overall improvement in cardiac efficiency. (wikipedia.org)
Thus due to the unique cardiac myosin activation mechanism, omecamtiv mecarbil could safely improve cardiac function within tolerated doses. (wikipedia.org)
Recently, research groups found that omecamtiv mecarbil actually inhibits myosin by enhancing the duty ratio, increasing calcium sensitivity and slowing force development. (wikipedia.org)
Omecamtiv mecarbil is a novel, selective cardiac myosin activator, also known as a cardiac myotrope, 2 that binds to the catalytic domain of myosin. (amgen.com)
Through the third study, Montefiore cardiologists are evaluating the effect of 48 hours of IV treatment with omecamtiv mecarbil (a novel, small-molecule, direct activator of cardiac myosin) in subjects with left ventricular systolic dysfunction who are hospitalized for acute heart failure. (montefiore.org)
Omecamtiv mecarbil: a myosin motor activator agent with promising clinical performance and new in vitro results. (sav.sk)
Omecamtiv mecarbil activates ryanodine receptors from canine cardiac but not skeletal muscle. (sav.sk)

In 2006, Cytokinetics and Amgen entered into a strategic alliance to discover, develop and commercialize novel small molecule therapeutics designed to activate the cardiac sarcomere for the potential treatment of heart failure. (amgen.com)
Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. (cytokinetics.com)
As a leader in muscle biology, we have a robust pipeline of small molecule muscle activators and inhibitors to address diseases characterized by compromised muscle function, including heart failure , hypertrophic cardiomyopathy (HCM Disease) , and neuromuscular diseases . (cytokinetics.com)

reldesemtiv, a fast-skeletal muscle troponin activator (FSTA) and CK-3773274 (CK-274), a cardiac myosin inhibitor. (stash.com)
This is highlighted by CK-274 advancement in REDWOOD-HCM and clinical development of a second myosin inhibitor. (biopharmajournal.com)
Clinical trials begin for the first potential cardiac myosin inhibitor. (cytokinetics.com)
First Phase 3 clinical trial of potential cardiac myosin inhibitor begins. (cytokinetics.com)

Preclinical research has shown that cardiac myotropes increase cardiac contractility without affecting intracellular myocyte calcium concentrations or myocardial oxygen consumption. (amgen.com)
We find that ceramide feeding or ceramide-elevating genetic manipulations are strongly associated with cardiac dilation and defects in contractility. (johnshopkins.edu)
Cardiac contractility is regulated by dynamic phosphorylation of sarcomeric proteins by kinases such as cAMP-activated protein kinase A (PKA). (biomedcentral.com)
Cardiac Myosin Binding Protein-C (cMyBPC) and cardiac troponin I (cTNI) are hypertrophic cardiomyopathy (HCM)-causing sarcomeric proteins which regulate contractility in response to PKA phosphorylation. (biomedcentral.com)
This study ascribes a novel function to MMGL isoform 4: it meets all criteria for classification as an AKAP, and we show that is involved in the phosphorylation of cMyBPC as well as cTNI, hence MMGL is an important regulator of cardiac contractility. (biomedcentral.com)
Originally thought to have only a structural role, cMyBPC has been shown to play an important role in the regulation of cardiac contractility [ 1 ], for which the N-terminal region of the protein appears to be crucial. (biomedcentral.com)
AMP-activated protein kinase phosphorylates cardiac troponin I and alters contractility of murine ventricular myocytes. (ox.ac.uk)
Treatment of cardiomyocytes with the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) resulted in increased myocyte contractility without changing the amplitude of Ca(2+) transient and prolonged relaxation despite shortening the time constant of Ca(2+) transient decay (tau). (ox.ac.uk)
In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. (cytokinetics.com)
We anticipate that these studies will decipher the molecular mechanisms of impaired myocardial contractility in a large group of cardiac patients and propose new treatments of chronic heart failure - a disease for which there is currently no effective treatment. (cardioweb.ru)

Danicamtiv is a novel myosin activator with promising preclinical data that is currently in clinical trials. (bvsalud.org)
Danicamtiv, the second direct myosin activator, has achieved encouraging results in preclinical and clinical studies, thus implicating its potential applicability in the treatment of heart failure with reduced ejection fraction (HFrEF). (unideb.hu)

Effects of danicamtiv, a novel cardiac myosin activator, in heart failure with reduced ejection fraction: experimental data and clinical results from a phase 2a trial. (nih.gov)
RESULTS: Danicamtiv increased force and calcium sensitivity via increasing the number of myosins in the ON state and slowing cross-bridge turnover. (bvsalud.org)
Danicamtiv corrected decreased calcium sensitivity in demembranated tissue, abnormal twitch magnitude and kinetics in intact cardiac tissue, and reduced ejection fraction in the whole organ. (bvsalud.org)
CONCLUSIONS: As demonstrated by the detailed studies of Danicamtiv, increasing myosin recruitment and altering cross-bridge cycling are 2 mechanisms to increase force and calcium sensitivity in cardiac muscle. (bvsalud.org)
Myosin activators such as Danicamtiv can treat the causative hypocontractile phenotype in genetic dilated cardiomyopathy. (bvsalud.org)
Taken together, danicamtiv improves cardiac systolic function, but it can also limit diastolic performance, especially at high drug concentrations. (unideb.hu)

METHODS AND RESULTS: A yeast 2-hybrid screen of a human heart cDNA library using the N-terminal 273 residues of γ2 as bait identified cardiac troponin I (cTnI) as a putative interactor. (ox.ac.uk)

This causes peripheral edema (blood pooling), which the sympathetic nervous system tries to correct by overstimulating the cardiac myocytes, leading to left ventricular hypertrophy, another characteristic of chronic heart failure. (wikipedia.org)
CardioFit® is an implantable congestive heart failure modulator that reduces the heart rate, improves ventricular volumes and restores regular cardiac rhythm. (montefiore.org)
Cardiac ventricular septation, besides its great intrinsic interest to evolutionary biologists, is also crucial to the physiologist and the clinician. (encyclopedia.pub)

The aim of this study is to investigate sesamin effects to diabetes-inducing cardiac hypertrophy. (spandidos-publications.com)
In the present study bioinformatics analysis demonstrated cardiac hypertrophy signaling may be the most important pathway for upregulating genes in sesamin-treated groups. (spandidos-publications.com)
Mutations affecting the regulatory γ2 subunit have been shown to cause an essentially cardiac-restricted phenotype of hypertrophy and conduction disease, suggesting a specific role for this subunit in the heart. (ox.ac.uk)

Current inotropic therapies work by increasing the force of cardiac contraction, such as through calcium conduction or modulating adrenoreceptors. (wikipedia.org)
Chemical energy in the form of ATP is converted into mechanical energy which allows myosin to strongly bind to actin and produce a power stroke resulting in sarcomere shortening/contraction. (wikipedia.org)
This enhances effective myosin cross-bridge formation and duration, while the velocity of contraction remains the same. (wikipedia.org)
3-5 Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into the mechanical force resulting in cardiac contraction. (amgen.com)
Hypothetically, MF30 should enhance the ON state of myosin, thereby increasing muscle contraction. (bvsalud.org)

Yet, previous observations found no effect of this antibody on actin sliding over myosin during in vitro motility assays with purified proteins in which myosin binding protein C (MyBPC) was absent. (bvsalud.org)
They identified several ceramide-interacting proteins, whose subsequent cardiac-specific manipulation can prevent LCM by altering caspase activation, sarcomeric maintenance, and lipogenesis. (johnshopkins.edu)
Using a broad spectrum anti-acetyl antibody, the researchers determined that one of the acetylated proteins is myosin. (cytoskeleton.com)
Recently, Foster et al 10 reported that in an initial acetylome of porcine heart proteins, 240 proteins were modified on 994 lysine residues with myosin acetylated on many different lysine amino acids. (cytoskeleton.com)

Systolic heart failure involves a loss of effective actin-myosin cross bridges in the myocytes (heart muscle cells) of the left ventricle, which leads to a decreased ability of the heart to move blood through the body. (wikipedia.org)
Cardiac myocytes contract through a cross-bridge cycle between the myofilaments, actin and myosin. (wikipedia.org)
Specifically, it increases the rate of phosphate release from myosin by stabilizing the pre-powerstroke and the phosphate release states, thereby accelerating the rate-determining step of the cross-bridge cycle, which is the transition of the actin-myosin complex from the weakly bound to the strongly bound state. (wikipedia.org)
MF30 is hypothesized to enhance the availability of myosin heads (subfragment-1 or S1) to bind actin by destabilizing the myosin S2 coiled-coil and sterically blocking S2 from binding S1. (bvsalud.org)
Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). (cytokinetics.com)
Modified lysine residues occurred in the actin binding region as well as the coiled-coil tail and the hinge regions of myosin (see Fig. 1). (cytoskeleton.com)
Note that acetylation covers all of the important functional areas of myosin from actin and ATP binding to the hinge region and even the coiled-coil tail. (cytoskeleton.com)

In fact, myosin is the most highly acetylated protein found to date with 49 acetylated lysine residues 10 . (cytoskeleton.com)
The relationship between MLCK and other myosin-activating protein kinases, in particular, protein kinase ROCK, in regulation of endothelial permeability is being studied. (cardioweb.ru)
When studying the properties of Kinase-Related Protein (KRP) from smooth muscles, which also exists as the C-terminal domain of MLCK, it was found that KRP / KRP domain interacts with myosin II, the main molecular motor of the cell. (cardioweb.ru)

There is a growing body of evidence which demonstrates that following ACS, microRNAs might inhibit fibroblast proliferation and scarring, as well as harmful apoptosis of cardiomyocytes, and stimulate fibroblast reprogramming into induced cardiac progenitor cells. (archivesofmedicalscience.com)

So far, no therapies for chronic HFrEF that specifically targeted systolic dysfunction have improved cardiac outcome. (pace-cme.org)
Cardiac causes include arrhythmias (tachycardia or bradycardia), structural heart disease, and myocardial dysfunction (systolic or diastolic). (medscape.com)

The MF30 monoclonal antibody, which binds to the myosin subfragment-2 (S2), was found to increase the extent of myofibril shortening. (bvsalud.org)

Recent cardiotropic drug developments have focused on cardiac myofilaments. (unideb.hu)

That means it should not exhaust the heart, which can occur with currently-used inotropic agents and contribute to cardiac ischaemia. (pharmatimes.com)

The importance of acetylation has recently been elevated by the utilization of histone deacetylase (HDAC) inhibitors in pre-clinical research and the treatment of hypertrophic heart disease 6,7 , as well as the discovery of several critical acetylated forms of myosin amino acids that need to be modified in order for the sarcomere to function correctly 8,9 . (cytoskeleton.com)
While studying HDAC inhibitors in cardiac function, Dr. Mahesh Gupta's laboratory showed that acetylation is important for sarcomere function. (cytoskeleton.com)

the cardiac isoform differs from its skeletal counterparts by containing an extra immunoglobulin-like (IgI) domain (C0) at the amino terminal, a charged residue-rich insertion in domain C5 and three phosphorylation sites in a motif between the second and third IgI domains (C1-C2), known as the MyBPC motif or m-domain. (biomedcentral.com)

We need to see whether the improvements in cardiac function translate into real benefits for patients, in terms of their symptoms and quality of life, and whether it can impact on mortality and morbidity. (pharmatimes.com)
To verify the bioinformatics prediction, sesamin was used as the main bioactive compound to attenuate the impact of diabetes induced by streptozotocin (STZ) on cardiac function in a rat model. (spandidos-publications.com)
Many classes of disorders can result in increased cardiac demand or impaired cardiac function. (medscape.com)
Additionally, to further elucidate the function of MMGL, we used it as bait to screen a cardiac cDNA library. (biomedcentral.com)
The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its long-term effects on cardiac structure and function. (cytokinetics.com)
In this review, we focus on the role of cardiomyocyte-derived and cardiac fibroblast-derived microRNAs that are involved in the regulation of genes associated with cardiomyocyte and fibroblast function and in atherosclerosis-related cardiac ischemia. (archivesofmedicalscience.com)
Heart failure develops when the heart, via an abnormality of cardiac function (detectable or not), fails to pump blood at a rate commensurate with the requirements of the metabolizing tissues or is able to do so only with an elevated diastolic filling pressure. (medscape.com)
Heart failure (see the images below) may be caused by myocardial failure but may also occur in the presence of near-normal cardiac function under conditions of high demand. (medscape.com)
Heart failure always causes circulatory failure, but the converse is not necessarily the case, because various noncardiac conditions (eg, hypovolemic shock, septic shock) can produce circulatory failure in the presence of normal, modestly impaired, or even supranormal cardiac function. (medscape.com)
Cardiac mitochondrial function is altered in a variety of inherited and acquired cardiovascular diseases. (jci.org)

Single, double, and triple-stained myofibrils with increasing amounts of antibodies against myosin rods indicate a possible competition with MyBPC. (bvsalud.org)

In heart failure, a history of an acute cardiac event or of progressive symptoms of heart failure is usually present. (medscape.com)

molecular disease regulates just more congestive than habitual management, including acetic in 32 Myosin of congestive hospitals, and while it may manage a better end than localized heart, it is extremely estimated with available nerve and poorer failure of procedure. (siriuspixels.com)

Given the prominence of myosin as a target for acetylation in cardiomyocytes, further biochemical and functional studies were undertaken. (cytoskeleton.com)

Assessment of cardiac risk in noncardiac surgery. (nih.gov)
With the advent of natriuretic peptide testing, differentiating cardiac from noncardiac causes of pulmonary edema has improved. (medscape.com)

resources: The cardiac coupling of the intrinsic boy vessels( atherosclerosis) of parts. (siriuspixels.com)

Overview of Cardiac Valvular Disorders Any heart valve can become stenotic or insufficient (also termed regurgitant or incompetent), causing hemodynamic changes long before symptoms. (msdmanuals.com)

Consistent with the hypothesis that MF30 competes with MyBPC binding to S2, cardiac tissue from MyBPC knockout mice was stained more intensely, especially in the C-zone, by MF30 compared to the wild type. (bvsalud.org)

The key to a good outcome in patients with cardiogenic shock is an organized approach, with rapid diagnosis and prompt initiation of pharmacologic therapy to maintain blood pressure and cardiac output and respiratory support, as well as reversal of the underlying cause. (medscape.com)

Cytokinetics recently released topline results of the study indicating that the cardiac myosin activator attained primary efficacy endpoint and also showed a significant effect in the reduction of cardiovascular death or heart failure. (biopharmajournal.com)
Atherosclerotic plaque rupture is the leading cause of cardiovascular death resulting from acute coronary syndrome (ACS) and leads to cardiac remodeling and fibrosis following ACS. (archivesofmedicalscience.com)

Insights towards the identification of cytosolic Ca2+-binding sites in ryanodine receptors from skeletal and cardiac muscle. (sav.sk)

It may still activate muscle as a whole however despite suppressing the working stroke of myosin. (wikipedia.org)
The Company is focused on discovering, developing and commercializing first-in-class muscle activators as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. (stash.com)

The first in a new class of drugs to treat heart failure called cardiac myosin activators has shown encouraging activity in a small Phase II trial published in The Lancet (August 20). (pharmatimes.com)
In elderly patients, fatigue and confusion can sometimes be the first symptoms of heart failure, which is related to a decrease in cardiac output. (medscape.com)
We identified several CIPs from mouse heart and Drosophila extracts, including caspase activator Annexin-X, myosin chaperone Unc-45, and lipogenic enzyme FASN1, and remarkably, their cardiac-specific manipulation can prevent LCM. (johnshopkins.edu)
This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure. (medscape.com)
Coronary sinus, normally located between the LEFT ATRIUM and LEFT VENTRICLE on the posterior surface of the heart, can serve as an anatomical reference for cardiac procedures. (bvsalud.org)

Moreover, the cardiac myosin activator tended to be more beneficial in HFrEF patients with a low LVEF. (pace-cme.org)
At any given time, Montefiore is actively recruiting patients for dozens of cardiac trials, including three new studies that began in 2011. (montefiore.org)
In advanced cases, patients can appear jaundiced because of cardiac cirrhosis. (medscape.com)
The company is looking forward to presenting the results at the AHA Scientific Sessions, which includes pre-specified subgroup analyses that will elaborate ion patients with different effects with the cardiac myosin activator. (biopharmajournal.com)
The causing bisoprolol of the written patients is that Ang II works failure stage by using the medical cardiac body, productions, culminating plasma requirement and living infection of depressive fluid. (siriuspixels.com)
It sustains also the treatment of failure, cardiac patients, and type. (siriuspixels.com)
All patients require admission to an intensive care setting, which may involve emergency transfer to the cardiac catheterization suite, critical care transport to a tertiary care center, or internal transfer to the intensive care unit (ICU). (medscape.com)

The increased cardiac output is independent of intracellular calcium and cAMP levels. (wikipedia.org)

Anatomy25

Organisms20

Diseases29

Chemicals and Drugs94

Analytical, Diagnostic and Therapeutic Techniques and Equipment35

Phenomena and Processes51

Disciplines and Occupations3

Information Science3

Health Care6

Omecamtiv11

Small molecule3

Inhibitor4

Contractility10

Preclinical2

Danicamtiv6

Troponin1

Ventricular3

Hypertrophy3

Contraction5

Proteins4

Actin7

Protein3

Apoptosis1

Dysfunction2

Binds1

Myofilaments1

Inotropic1

Inhibitors2

Phosphorylation1

Function10

Antibodies1

Acute cardiac1

Congestive1

Cardiomyocytes1

Noncardiac2

Atherosclerosis1

Disorders1

MyBPC1

Respiratory1

Cardiovascular2

Skeletal1

Muscle2

Heart5

Patients7

Intracellular1